Publications by authors named "Chaozhao Liang"

168 Publications

Targeting the Lnc-OPHN1-5/androgen receptor/hnRNPA1 complex increases Enzalutamide sensitivity to better suppress prostate cancer progression.

Cell Death Dis 2021 Sep 20;12(10):855. Epub 2021 Sep 20.

George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, The Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.

Long non-coding RNAs (lncRNAs) have been found to play critical roles in regulating gene expression, but their function in translational control is poorly understood. We found lnc-OPHN1-5, which lies close to the androgen receptor (AR) gene on chromosome X, increased prostate cancer (PCa) Enzalutamide (Enz) sensitivity via decreasing AR protein expression and associated activity. Mechanism dissection revealed that lnc-OPHN1-5 interacted with AR-mRNA to minimize its interaction with the RNA binding protein (RBP) hnRNPA1. Suppressing lnc-OPHN1-5 expression promoted the interaction between AR-mRNA and hnRNPA1, followed by an increase of ribosome association with AR-mRNA and translation. This effect was reversed by increasing lnc-OPHN1-5 expression. Consistently, the in vivo mice model confirmed that knocking down lnc-OPHN1-5 expression in tumors significantly increased the tumor formation rate and AR protein expression compared with the control group. Furthermore, knocking down hnRNPA1 blocked/reversed shlnc-OPHN1-5-increased AR protein expression and re-sensitized cells to Enz treatment efficacy. Evidence from Enz-resistant cell lines, patient-derived xenograft (PDX) models, clinical samples, and a human PCa study accordantly suggested that patients with low expression of lnc-OPHN1-5 likely have unfavorable prognoses and probably are less sensitive to Enz treatment. In summary, targeting this newly identified lnc-OPHN1-5/AR/hnRNPA1 complex may help develop novel therapies to increase Enz treatment sensitivity for suppressing the PCa at an advanced stage.
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http://dx.doi.org/10.1038/s41419-021-03966-4DOI Listing
September 2021

A costimulatory molecule-related signature in regard to evaluation of prognosis and immune features for clear cell renal cell carcinoma.

Cell Death Discov 2021 Sep 18;7(1):252. Epub 2021 Sep 18.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Costimulatory molecules have been proven to enhance antitumor immune responses, but their roles in clear cell renal cell carcinoma (ccRCC) remain unexplored. In this study, we aimed to explore the gene expression profiles of costimulatory molecule genes in ccRCC and construct a prognostic signature to improve treatment decision-making and clinical outcomes. We performed the first comprehensive analysis of costimulatory molecules in patients with ccRCC and identified 13 costimulatory molecule genes with prognostic values and diagnostic values. Consensus clustering analysis based on these 13 costimulatory molecular genes showed different distribution patterns and prognostic differences for the two clusters identified. Then, a costimulatory molecule-related signature was constructed based on these 13 costimulatory molecular genes, and validated in an external dataset, showing good performance for predicting a patient's prognosis. The signature was an independent risk factor for ccRCC patients and was significantly correlated with patients' clinical factors, which could be used as a complement for clinical factors. In addition, the signature was associated with the tumor immune microenvironment and the response to immunotherapy. Patients identified as high-risk based on our signature exhibited a high mutation frequency, a high level of immune cell infiltration, and an immunosuppressive microenvironment. High-risk patients tended to have high cytolytic activity scores and immunophenoscore of CTLA4 and PD1/PD-L1/PD-L2 blocker than low-risk patients, suggesting these patients may be more suitable for immunotherapy. Therefore, our signature could provide clinicians with prognosis predictions and help guide treatment for ccRCC patients.
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http://dx.doi.org/10.1038/s41420-021-00646-2DOI Listing
September 2021

N-Myc promotes angiogenesis and therapeutic resistance of prostate cancer by TEM8.

Med Oncol 2021 Sep 14;38(10):127. Epub 2021 Sep 14.

Department of Pathology, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, People's Republic of China.

Although patients with early localized prostate cancer can survive longer, castration-resistant prostate cancer (CRPC) has gradually emerged with the use of androgen deprivation therapy (ADT). N-Myc and TEM8 play a vital role in the progression of several cancer types. However, the underlying mechanism of how N-Myc and TEM8 promote the progression of prostate cancer remains unclear. In this study, the expression of N-Myc and TEM8 was detected in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues by immunohistochemistry (IHC). LNCaP cell lines were maintained in RPMI 1640 medium supplemented with 10% charcoal-stripped fetal bovine serum. Subsequently, R language software was used to verify our results. Tubule formation assay of human umbilical vein endothelial cell (HUVEC) was conducted to examine the effect of N-Myc and TEM8 overexpression on angiogenesis in prostate cancer cells. IHC results showed a positive correlation between the expression of N-Myc and TEM8 in prostate cancer tissues. Further analysis showed that N-Myc and TEM8 were associated with clinicopathological features and poor prognosis in prostate cancer patients. Moreover, the overexpression of N-Myc and TEM8 promoted proliferation of prostate cancer cells and angiogenesis. Additionally, N-Myc and TEM8 overexpression was associated with therapeutic resistance. We further found that N-Myc promoted angiogenesis and therapeutic resistance in prostate cancer via TEM8. Hence, targeting N-Myc/TEM8 pathway in prostate cancer would be a novel therapeutic strategy to enhance the treatment of prostate cancer patients.
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http://dx.doi.org/10.1007/s12032-021-01575-xDOI Listing
September 2021

Chronic Prostatitis and Pelvic Pain Syndrome: Another Autoimmune Disease?

Arch Immunol Ther Exp (Warsz) 2021 Sep 14;69(1):24. Epub 2021 Sep 14.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by chronic pain in the perineum or lower abdomen regions, is a frequent disorder in men. Previous studies demonstrated that the immune mediators, including interleukin (IL)-1β, IL-6, interferon-γ, tumor necrosis factor-α, and immunoglobulins, are elevated in the expressed prostate secretions and seminal fluid of CP/CPPS men. The memory T, T helper 1 (Th1), Th17, and Th22 cells increase in the peripheral blood of CP/CPPS men. Additionally, prostate antigens specific-autoreactive T cells are identified in CP/CPPS patients. After generally reviewing and comparing the inflammatory responses in autoimmune diseases and CP/CPPS, we presumed that CP/CPPS is more likely to be defined as an autoimmune disease. Thus, a better understanding of autoimmune diseases would contribute to a deeper understanding of the CP/CPPS and provide new inspirations for the treatment of this disease.
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http://dx.doi.org/10.1007/s00005-021-00628-3DOI Listing
September 2021

XIST Inhibition Attenuates Calcium Oxalate Nephrocalcinosis-Induced Renal Inflammation and Oxidative Injury via the miR-223/NLRP3 Pathway.

Oxid Med Cell Longev 2021 2;2021:1676152. Epub 2021 Sep 2.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The roles of the lncRNA X inactive specific transcript (XIST) in many diseases, including cancers and inflammatory sickness, have been previously elucidated. However, renal calculus remained poorly understood. In this study, we revealed the potential effects of XIST on kidney stones that were exerted via inflammatory response and oxidative stress mechanisms. We established a glyoxylate-induced calcium oxalate (CaOx) stone mouse model and exposed HK-2 cells to calcium oxalate monohydrate (COM). The interactions among XIST, miR-223-3p, and NOD-like receptor protein 3 (NLRP3) and their respective effects were determined by RNAs and protein expression, luciferase activity, and immunohistochemistry (IHC) assays. Cell necrosis, reactive oxygen species (ROS) generation, and inflammatory responses were detected after silencing XIST, activating and inhibiting miR-223-3p, and both knocking down XIST and activating miR-223-3p in vitro and in vivo. The XIST, NLRP3, caspase-1, and IL-1 levels were notably increased in kidney samples from glyoxylate-induced CaOx stone model mice. XIST knockdown significantly suppressed the inflammatory damage and ROS production and further attenuated oxalate crystal deposition. miRNA-223-3p mimics also exerted the same effects. Moreover, we verified the interactions among XIST, miRNA-223-3p and NLRP3, and the subsequent effects. Our results suggest that the lncRNA XIST participates in the formation and progression of renal calculus by interacting with miR-223-3p and the NLRP3/Caspase-1/IL-1 pathway to mediate the inflammatory response and ROS production.
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http://dx.doi.org/10.1155/2021/1676152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429007PMC
September 2021

Prognostic Value of the Systemic Inflammatory Response Index in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Population-Based Study.

Front Oncol 2021 16;11:722151. Epub 2021 Aug 16.

Department of Urology, Shanghai Tenth People's Hospital, Tongi University, Shanghai, China.

Purpose: The aim of this study was to evaluate the prognostic significance of the systemic inflammatory response index (SIRI) in patients with bladder cancer (BCa) treated with radical cystectomy (RC) and develop a survival predictive model through establishing a nomogram.

Materials And Methods: A total of 203 BCa patients who underwent RC were included in this study. The relationship between the SIRI and overall survival (OS), disease-free survival (DFS), and clinicopathological features were evaluated. Cox regression analysis was performed to investigate the effect of the factors on the OS and DFS. The results were applied in the establishment of a nomogram. Receiver operating characteristic (ROC) curves, decision curve analysis (DCA) curves, and calibration curves were performed to assess the predictive performance and accuracy of the nomogram, respectively.

Results: According to the classification of the SIRI, 81 patients (39.9%) were assigned to SIRI grade 1, 94 patients (46.3%) to SIRI grade 2, and the remaining 28 patients (13.8%) to SIRI grade 3. Multivariate Cox regression revealed that a higher SIRI grade was significantly associated with a poor prognosis and served as an independent prognostic factor for the OS [Grade 2 Grade 1, odds ratio = 2.54, 95% confidence interval (CI),1.39-4.64, P = 0.002; Grade 3 Grade 1, odds ratio = 4.79, 95%CI: 2.41-9.50, P < 0.001] and DFS [Grade 2 Grade 1, odds ratio = 2.19, 95% CI, 1.12-4.31, P = 0.023; Grade 3 Grade 2, odds ratio = 3.36, 95%CI, 1.53-7.35, P = 0.002]. The ROC and DCA analysis indicated that the nomogram based on the SIRI contained a better predictive performance compared with the TNM stage (AUC = 0.750 and 0.791; all P < 0.05). The ROC analysis showed that nomograms can better predict the 3- and 5-year OS and DFS. The calibration curves exhibited a significant agreement between the nomogram and the actual observation.

Conclusion: SIRI as a novel independent prognostic index and potential prognostic biomarker can effectively improve the traditional clinicopathological analysis and optimize individualized clinical treatments for BCa patients after RC.
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http://dx.doi.org/10.3389/fonc.2021.722151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416169PMC
August 2021

Identification of a Costimulatory Molecule-Related Signature for Predicting Prognostic Risk in Prostate Cancer.

Front Genet 2021 16;12:666300. Epub 2021 Aug 16.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Costimulatory molecules have been proven to enhance antitumor immune responses, but their roles in prostate cancer (PCa) remain unexplored. In this study, we aimed to explore the gene expression profiles of costimulatory molecule genes in PCa and construct a prognostic signature to improve treatment decision making and clinical outcomes. Five prognosis-related costimulatory molecule genes (RELT, TNFRSF25, EDA2R, TNFSF18, and TNFSF10) were identified, and a prognostic signature was constructed based on these five genes. This signature was an independent prognostic factor according to multivariate Cox regression analysis; it could stratify PCa patients into two subgroups with different prognoses and was highly associated with clinical features. The prognostic significance of the signature was well validated in four different independent external datasets. Moreover, patients identified as high risk based on our prognostic signature exhibited a high mutation frequency, a high level of immune cell infiltration and an immunosuppressive microenvironment. Therefore, our signature could provide clinicians with prognosis predictions and help guide treatment for PCa patients.
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http://dx.doi.org/10.3389/fgene.2021.666300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415313PMC
August 2021

Associations of IL-17A -197G/A and IL-17F 7488T/C polymorphisms with cancer risk in asians: An updated meta-analysis from 43 studies.

Gene 2021 Dec 14;804:145901. Epub 2021 Aug 14.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address:

Objective: Numerous epidemiological studies have been published to elucidate the potential associations of IL-17A -197G/A (rs2275913) and IL-17F 7488T/C (rs763780) with cancer risk in Asians. Nevertheless, the results from different studies remain controversial. To identify the roles of the two polymorphisms in cancer risk, we performed this current meta-analysis.

Methods: The available literature was derived from five databases, covering relevant articles updated through February 17, 2021. Five different analysis models with corresponding odds ratios (ORs) and 95% confidence intervals (CIs) were applied to appraise the gene-disease correlation.

Results: In total, 43 case-control studies with 31,237 subjects were enrolled. Overall analyses indicated that there was significantly increased cancer risk led by IL-17A -197G/A under the five analysis models. A similar tendency was also identified in the subgroup analysis of cancer type, especially for gastric cancer, cervical cancer, colorectal cancer, and oral carcinoma. As for IL-17F 7488T/C, we revealed that patients who carried this variant had a higher cancer risk in the recessive model among the overall analyses, as well as subgroup analyses of cervical cancer or oral carcinoma.

Conclusions: In summary, our work confirmed that IL-17A -197G/A acted as a risk factor for diverse cancer types and that IL-17F 7488T/C might be involved in cervical cancer and oral carcinoma.
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http://dx.doi.org/10.1016/j.gene.2021.145901DOI Listing
December 2021

4-Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy for chronic prostatitis.

Prostate 2021 Oct 28;81(14):1078-1090. Epub 2021 Jul 28.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology, and Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, China.

Background: Hyaluronan (HA), an extracellular matrix component, accumulates in most chronic inflammatory tissues. Here, we studied the impact of HA on the pathogenesis of chronic prostatitis.

Materials And Methods: First, we sorted demographic characteristics and peripheral blood serum samples from patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to assess the relationship between the levels of HA in peripheral blood serum and the severity of inflammation in patients. Second, we induced an experimental autoimmune prostatitis (EAP) mouse model and treated the mice with 4-methylumbelliferone (4-MU) (200 mg/kg/day). After the mice were sacrificed, RNA from Th1 cells of the mouse spleens was extracted for RNA sequencing. We used weighted gene co-expression network analysis (WGCNA) to identify co-expressed gene modules and hub-gene related to the pathogenesis of EAP. The expression of critical genes associated with the identified pathway was confirmed by using western blot analysis.

Results: HA was significantly more highly expressed in CP/CPPS patients than in healthy volunteers and positively correlated with the severity of pain, urination symptoms, and quality of life. Besides, the protein expression of HA was significantly higher in prostate tissues derived from EAP models than in those derived from controls. 4-MU, an oral inhibitor of HA synthesis, relieved immunocyte infiltration to the prostate and significantly reduced the proportion of Th1 cells. Based on the WGCNA, we identified 18 co-expression modules and identified that the Grey60 and brown modules were positively associated with the EAP and negatively associated with the Control and 4-MU-treated groups. Pathway enrichment analyses and western blot assays proved that HA potentially activated the cell cycle pathway, increasing the proportion of Th1 cells promoting chronic prostatitis pathogenesis, while these processes were reversed by 4-MU treatment.

Conclusions: Our results suggest that HA is elevated in patients with CP/CPPS compared with healthy controls and that targeting HA through 4-MU suppresses the activity of the cell cycle-related pathway, potentially by decreasing the proportion of Th1 cells and relieving chronic prostatitis. Our findings might inspire the clinical treatment of chronic prostatitis.
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http://dx.doi.org/10.1002/pros.24205DOI Listing
October 2021

Clinical efficacy of low-dose emetine for patients with COVID-19: a real-world study.

J BioX Res 2021 Jun 3;4(2):53-59. Epub 2020 Dec 3.

Anhui Feidong County People's Hospital.

Objective: Emetine, an isoquinoline alkaloid that is enriched at high concentrations in the lung, has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019 (COVID-19).

Methods: In this real-world study, 63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province, China from February to March 2020. Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial, and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study. The medication course of emetine was less than 10 days. The main symptoms and adverse reactions of all patients were observed and recorded. The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10. Secondary outcomes included axillary temperature, transcutaneous oxygen saturation, and respiratory frequency recovery. The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20, 2019 (approval No. PJ2020-03-19) and was registered with the Chinese Clinical Trial Registry on February 20, 2019 (registration number: ChiCTR2000030022).

Results: The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital. The axillary body temperature, respiratory rate, and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures. The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect. The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.

Conclusion: Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects, suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.
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http://dx.doi.org/10.1097/JBR.0000000000000076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237841PMC
June 2021

Recurrent Prostatic Stromal Tumor of Uncertain Malignant Potential Combined with Concurrent Prostatic Adenocarcinoma: An Unusual Case.

Urol Int 2021 Jul 6:1-5. Epub 2021 Jul 6.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Prostatic stromal tumor of uncertain malignant potential (STUMP), characterized by an atypical, unique stromal proliferation of the prostate, is often difficult to be differentiated from other nonepithelial neoplastic lesions. We present a unique case of recurrent STUMP after transurethral resection of the prostate (TURP) with concurrent prostatic adenocarcinoma. Patients diagnosed with prostatic STUMP should be followed up closely, for it may recur and invade adjacent organs after TURP shortly. Concurrent prostatic adenocarcinoma can be found in STUMP patients, and there may be some potential mechanisms which promote the simultaneous occurrence of the 2 tumors.
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http://dx.doi.org/10.1159/000511652DOI Listing
July 2021

Prognosis stratification and personalized treatment in bladder cancer through a robust immune gene pair-based signature.

Clin Transl Med 2021 06;11(6):e453

State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, 211198, P.R. China.

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http://dx.doi.org/10.1002/ctm2.453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214857PMC
June 2021

Application of Contrast-Enhanced Ultrasonography (CEUS) in the Assessment of Kidney Wound Recovery After Nephron-Sparing Surgery.

Cancer Manag Res 2021 13;13:3925-3934. Epub 2021 May 13.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.

Purpose: To investigate feasibility, repeatability and usefulness of contrast-enhanced ultrasonography (CEUS) in the assessment of kidney wound recovery after laparoscopic nephron-sparing surgery (LNSS) or robot-assisted nephron-sparing surgery (RANSS) and preliminarily research the clinical factors associated with the length of extravasation (LOE).

Patients And Methods: From April 2019 to January 2020, 130 patients that underwent LNSS or RANSS in our hospital were included, and 90 patients (90/130) received CEUS examinations each one day from the postoperative day 1. The discovery of the cessation of contrast medium extravasation from the renal wound was the primary endpoint named "ultrasonic healing", and LOE ranged from the day of surgery to "ultrasonic healing". Patient, tumor, perioperative factors and LOE were collected. Univariate analysis and multivariate linear regression analysis were applied for the determination of factors associated with LOE.

Results: The average postoperative LOE was 1.76 days (standard deviation, 1.115; 95% confidence interval: 1.52-1.99). Ultrasonic healing within three days was observed in 95.6% patients (86/90). Univariable and multivariable analyses showed that R and A components in R.E.N.A.L. nephrometry score were associated with LOE. Anterior location and R component score of 2 (tumor size>4cm) were related to longer LOE than posterior location and R score of 1 (tumor size<4cm). The incidence of complications in patients with LOE over one day was higher than those with LOE of one day.

Conclusion: CEUS was feasible, repeatable and useful in the assessment of kidney wound recovery. Tumor size and location were related to LOE after minimally invasive nephron-sparing surgery (MINSS). Length of stay after MINSS within three days might be relatively safe.
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http://dx.doi.org/10.2147/CMAR.S297270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130454PMC
May 2021

hsa_circ_0062019 promotes the proliferation, migration, and invasion of prostate cancer cells via the miR-195-5p/HMGA2 axis.

Acta Biochim Biophys Sin (Shanghai) 2021 Jul;53(7):815-822

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

Circular RNA (circRNA) is a new class of non-coding RNA. It was reported that circRNA involves in the metastasis of cancer. The aim of this study is to explore the role and mechanism of circRNA hsa_circ_0062019 in the development of prostate cancer (PCa). Our results showed that hsa_circ_0062019 was highly expressed in PCa cell lines. Cell Counting Kit-8 assay revealed that upregulation of hsa_circ_0062019 boosted PCa cell proliferation, and silencing of hsa_circ_0062019 inhibited cell proliferation. Meanwhile, transwell assay proved that upregulation of hsa_circ_0062019 facilitated PCa cell invasion and migration, while downregulation of hsa_circ_0062019 inhibited these malignant phenotypes. Furthermore, luciferase reporter assay proved the binding of hsa_circ_0062019 with miR-195-5p and the binding between miR-195-5p and high mobility group AT-hook 2 (HMGA2), suggesting that hsa_circ_0062019 promoted the expression of HMGA2 by sponging miR-195-5p. In addition, our results revealed that the hsa_circ_0062019-induced PCa cell malignant phenotypes were notably reversed by the downregulation of HMGA2. Overall, our study demonstrated that hsa_circ_0062019 promoted PCa cell proliferation, migration, and invasion via upregulation of HMGA2 expression by sponging miR-195-5p. Our study proved a novel molecular mechanism of PCa development and provided a potential target for the treatment of PCa.
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http://dx.doi.org/10.1093/abbs/gmab058DOI Listing
July 2021

Li-ESWT treatment reduces inflammation, oxidative stress, and pain via the PI3K/AKT/FOXO1 pathway in autoimmune prostatitis rat models.

Andrology 2021 May 7. Epub 2021 May 7.

Institute of Urology, Key Laboratory of Gansu Urological Diseases, Gansu Nephro-Urological Clinical Center, Lanzhou University Second Hospital, Lanzhou, China.

Background: Due to limited data on the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the suboptimal therapeutic effect, the development of new and effective treatment modalities was needed urgently. Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported for the treatment of CP/CPPS. However, the underlying mechanism remains to be elucidated.

Objective: To interrogated the efficacy and the mechanism of Li-ESWT in the treatment of CP/CPPS.

Materials And Methods: According to different treatments, RWPE-1 cells (human prostate epithelial cells) were randomly divided into three groups: control group, LPS (lipopolysaccharide) group, or Li-ESWT group (LPS-induced RWPE-1 managed by Li-ESWT). Following the Li-ESWT treatment, the levels of oxidative stress were assayed. We then established a rat model of experimental autoimmune prostatitis (EAP) by injecting prostatic protein homogenate mixed with complete Freund's adjuvant. The Sprague-Dawley rats were randomly divided into the control group, EAP group, or Li-ESWT group. Von Frey Filament was used to quantify pelvic hyperalgesia in the rats. Prostates tissues from each group were collected for immunohistochemistry, oxidation stress, and Western blot analysis.

Results: Histological analysis showed reduced inflammation and expression of cytokines (TNF-α, IL-1β, IL-6, COX-2, SP) in prostate tissues from the Li-ESWT group compared with those from the EAP group (all p < 0.05). Similarly, there was reduced pelvic pain and allergic symptoms in the Li-ESWT group compared with the EAP group (all p < 0.05). Besides, Li-ESWT treatment could decrease oxidative stress in the prostate and in RWPE-1 cells, respectively (both p < 0.05). Moreover, the Li-ESWT upregulated the expression of CAT through the inhibition of phosphorylation of AKT/FOXO1 signaling pathway.

Discussion And Conclusions: Li-ESWT may reduce inflammation, oxidative stress, and pain in rats with autoimmunity-induced prostatitis via the PI3 K/AKT/FOXO1 pathway. It implies that Li-ESWT can present a potential therapeutic option for the treatment of CP/CPPS.
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http://dx.doi.org/10.1111/andr.13027DOI Listing
May 2021

Exosomal LINC00355 derived from cancer-associated fibroblasts promotes bladder cancer cell proliferation and invasion by regulating miR-15a-5p/HMGA2 axis.

Acta Biochim Biophys Sin (Shanghai) 2021 May;53(6):673-682

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

We have previously demonstrated that exosomes derived from cancer-associated fibroblasts (CAFs) promote bladder cancer (BC) cell proliferation and invasion by transferring LINC00355. In this study, the molecular mechanisms underlying the pro-bladder cancer action of exosomal LINC00355 were explored. CAFs were obtained from BC tumor tissues, and normal fibroblasts (NFs) were obtained from adjacent normal tissues. Human BC cell lines (T24 and 5367) were incubated with NF-Exo (exosomes from NFs), CAF-Exo (exosomes from CAFs), CAFsi-Ctrl-Exo (exosomes from si-Ctrl-transfected CAFs), and CAFsi-LINC00355-Exo (exosomes from si-LINC00355-transfected CAFs). BC cell proliferation and invasion were evaluated by MTT and Transwell assays, respectively. The interaction between miR-15a-5p and LINC00355 or HMGA2 was examined by online bioinformatics analysis and luciferase activity assay. Results showed that HMGA2 is a direct target of miR-15a-5p, and LINC00355 functions as a sponge of miR-15a-5p to upregulate HMGA2 expression. The promoting effects of CAF-Exo on HMGA2 expression, cell proliferation, and cell invasion were hindered when LINC00355 expression was inhibited in BC cells. These promoting effects were also hindered when miR-15a-5p was overexpressed or HMGA2 was silenced in BC cells. In conclusion, exosomal LINC00355 derived from CAFs promotes BC cell proliferation and invasion by regulating miR-15a-5p/HMGA2 axis.
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http://dx.doi.org/10.1093/abbs/gmab041DOI Listing
May 2021

Construction of Competitive Endogenous RNA Network and Verification of 3-Key LncRNA Signature Associated With Distant Metastasis and Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma.

Front Oncol 2021 24;11:640150. Epub 2021 Mar 24.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Clear cell renal cell carcinoma (ccRCC) is a common malignancy with high distant metastasis rate. Long non-coding RNAs (LncRNAs) are reported to be upregulated or downregulated in multiple cancers and play a crucial role in the metastasis of tumors or prognosis. Therefore, the purpose of our study is to construct a prognostic signature for ccRCC based on distant metastasis-related lncRNAs and explore the involved potential competitive endogenous RNA (ceRNA) network. The differentially expressed genes (DEGs) screened from the database of the cancer genome atlas (TCGA) were used to construct a co-expression network and identify the distant metastasis-related module by weighted gene co-expression network analysis (WGCNA). Key genes with metastatic and prognostic significance were identified through rigorous screening, including survival analysis, correlation analysis, and expression analyses in stage, grade, and distant metastasis, and were verified in the data set of gene expression omnibus (GEO) and the database from gene expression profiling interactive analysis (GEPIA). The potential upstream miRNAs and lncRNAs were predicted five online databases and LncBase. Here, we constructed a ceRNA network of key genes that are significantly associated with the distant metastasis and prognosis of patients with ccRCC. The distant metastasis-related lncRNAs were used to construct a risk score model through the univariate, least absolute shrinkage selection operator (LASSO), and multivariate Cox regression analyses, and the patients were divided into high- and low-risk groups according to the median of the risk score. The Kaplan-Meier survival analysis demonstrated that mortality was significantly higher in the high-risk group than in the low-risk group. Considering the other clinical phenotype, the Cox regression analyses indicated that the lncRNAs model could function as an independent prognostic factor. Quantitative real-time (qRT)-PCR in the tissues and cells of ccRCC verified the high-expression level of three lncRNAs. Gene set enrichment analysis (GSEA) revealed that the lncRNA prognostic signature was mainly enriched in autophagy- and immune-related pathways, indicating that the autophagy and immune functions may play an important role in the distant metastasis of ccRCC. In summary, the constructed distant metastasis-related lncRNA signature could independently predict prognosis in patients with ccRCC, and the related ceRNA network provided a new sight on the potential mechanism of distant metastasis and a promising therapeutic target for ccRCC.
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http://dx.doi.org/10.3389/fonc.2021.640150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044754PMC
March 2021

Exosomal LINC00355 derived from cancer-associated fibroblasts promotes bladder cancer cell resistance to cisplatin by regulating miR-34b-5p/ABCB1 axis.

Acta Biochim Biophys Sin (Shanghai) 2021 Apr;53(5):558-566

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

Cisplatin resistance is a major challenge for bladder cancer (BC). Evidence indicates that exosome derived from cancer-associated fibroblasts (CAF-Exo) can promote chemotherapy resistance in various human tumors by delivering bioactive molecules. We have previously demonstrated that CAF-derived exosomal LINC00355 promotes BC cell proliferation and invasion. However, the underlying mechanisms are still unclear. In this study, we aimed to investigate the role and mechanisms of CAF-derived exosomal LINC00355 in BC cell resistance to cisplatin. Exosomes were isolated from normal fibroblasts (NFs) and BC tumor-derived CAFs, namely, NF-Exo and CAF-Exo. CAFs were transfected with si-Ctrl or si-LINC00355 and then different exosomes were isolated, namely, CAFsi-Ctrl-Exo and CAFsi-LINC00355-Exo. The human BC cell lines (T24 and 5367) were incubated with NF-Exo, CAF-Exo, CAFsi-Ctrl-Exo, and CAFsi-LINC00355-Exo in the presence of cisplatin. MTT proliferation assay and flow cytometric analysis showed that CAF-Exo promoted BC cell resistance to cisplatin and upregulated ABCB1 expression in BC cells by transferring LINC00355 to BC cells. Luciferase activity assay confirmed the interaction between miR-34b-5p and LINC00355 or ABCB1. qRT-PCR and western blot analysis further showed that LINC00355 sponged miR-34b-5p to upregulate ABCB1 expression. However, the promoting effects of CAF-Exo on BC cell resistance to cisplatin were abolished by miR-34b-5p overexpression and ABCB1 silencing. In conclusion, exosomal LINC00355 derived from CAFs promotes BC cell resistance to cisplatin by regulating the miR-34b-5p/ABCB1 axis.
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http://dx.doi.org/10.1093/abbs/gmab023DOI Listing
April 2021

Tumor immune microenvironment-based classifications of bladder cancer for enhancing the response rate of immunotherapy.

Mol Ther Oncolytics 2021 Mar 4;20:410-421. Epub 2021 Feb 4.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology, Anhui Medical University, Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei 230022, P.R. China.

Immunotherapy is a potential way to save the lives of patients with bladder cancer, but it only benefits approximately 20% of them. A total of 4,028 bladder cancer patients were collected for this study. Unsupervised non-negative matrix factorization and the nearest template prediction algorithms were employed for the classification. We identified the immune and non-immune classes from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA-BLCA) training cohort. The 150 most differentially expressed genes between these two classes were extracted, and the classification reappeared in 20 validation cohorts. For the activated and exhausted subgroups, a stromal activation signature was assessed by the NTP algorithm. Patients in the immune class showed highly enriched signatures of immunocytes, while the exhausted subgroup also exhibited activated transforming growth factor (TGF)-β1, and cancer-associated extracellular matrix signatures. Patients in the immune-activated subgroup showed a lower genetic alteration and better overall survival. Anti-PD-1/PD-L1 immunotherapy was more beneficial for the immune-activated subgroup, while immune checkpoint blockade therapy plus a TGF-β inhibitor or an EP300 inhibitor might achieve greater efficacy for patients in the immune-exhausted subgroup. Novel immune molecular classifier was identified for the innovative immunotherapy of patients with bladder cancer.
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http://dx.doi.org/10.1016/j.omto.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900642PMC
March 2021

Health-related quality of life of COVID-19 patients after discharge: A multicenter follow-up study.

J Clin Nurs 2021 Jun 17;30(11-12):1742-1750. Epub 2021 Mar 17.

Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China.

Aims And Objectives: To determine the health-related quality of life (HRQoL) of COVID-19 patients after discharge and its predicting factors.

Background: COVID-19 has caused a worldwide pandemic and led a huge impact on the health of human and daily life. It has been demonstrated that physical and psychological conditions of hospitalised COVID-19 patients are impaired, but the studies focus on physical and psychological conditions of COVID-19 patients after discharge from hospital are rare.

Design: A multicentre follow-up study.

Methods: This was a multicentre follow-up study of COVID-19 patients who had discharged from six designated hospitals. Physical symptoms and HRQoL were surveyed at first follow-up (the third month after discharge). The latest multiple laboratory findings were collected through medical examination records. This study was performed and reported in accordance with STROBE checklist.

Results: Three hundred eleven patients (57.6%) were reported with one or more physical symptoms. The scores of HRQoL of COVID-19 patients at third month after discharge, except for the dimension of general health, were significantly lower than Chinese population norm (p < .001). Results of logistic regression showed that female (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.04-3.06), older age (≥60 years) (OR: 2.44, 95% CI: 1.33-4.47) and the physical symptom after discharge (OR: 40.15, 95% CI: 9.68-166.49) were risk factors for poor physical component summary; the physical symptom after discharge (OR: 6.68, 95% CI: 4.21-10.59) was a risk factor for poor mental component summary.

Conclusions: Health-related quality of life of discharged COVID-19 patients did not come back to normal at third month after discharge and affected by age, sex and the physical symptom after discharge.

Relevance To Clinical Practice: Healthcare workers should pay more attention to the physical and psychological rehabilitation of discharged COVID-19 patients. Long-term follow-up on COVID-19 patients after discharge is needed to determine the long-term impact of COVID-19.
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http://dx.doi.org/10.1111/jocn.15733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013595PMC
June 2021

Integrated Analysis Revealed the MicroRNA-Based Prognostic Predicting Signature for Papillary Renal Cell Carcinoma.

DNA Cell Biol 2021 Mar 22;40(3):532-542. Epub 2021 Feb 22.

Department of Urology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Renal cell carcinoma (RCC) is one of the most frequently occurring tumors worldwide. Herein, we established a microRNA (miRNA) predicting signature to assess the prognosis of papillary-type RCC (PRCC) patients. miR-1293, miR-34a, miR-551b, miR-937, miR-299, and miR-3199-2 were used in building the overall survival (OS)-related signature, whereas miR-7156, miR-211, and miR-301b were used to construct the formula of recurrence-free survival (RFS) with the help of LASSO Cox regression analysis. The Kaplan-Meier and receiver operating characteristic curves indicated good discrimination and efficiency of the two signatures. Functional annotation for the downstream genes of the OS/RFS-related miRNAs exposed the potential mechanisms of PRCC. Notably, the multivariate analyses suggested that the two signatures were independent risk factors for PRCC patients and had better prognostic capacity than any other classifier. In addition, the nomogram indicated synthesis effects and showed better predictive performance than clinicopathologic features and our signatures. We validated the OS and RFS prediction formulas in clinical samples and met our expectations. Finally, we established two novel miRNA-based OS and RFS predicting signatures for PRCC, which are reliable tools for assessing the prognosis of PRCC patients.
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http://dx.doi.org/10.1089/dna.2019.5306DOI Listing
March 2021

3-Bromopyruvate decreased kidney fibrosis and fibroblast activation by suppressing aerobic glycolysis in unilateral ureteral obstruction mice model.

Life Sci 2021 May 9;272:119206. Epub 2021 Feb 9.

Department of Urology, Institute of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei City 230022, Anhui Province, China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei City 230032, Anhui Province, China. Electronic address:

Aims: Enhanced aerobic glycolysis is a motivation of fibroblast-myofibroblast transdifferentiation (FMT), leading to kidney fibrosis. 3-Bromopyruvate (3-BrPA) is a glycolysis inhibitor and has fibrosis-protected effect in liver. This study aims to explore the effects of 3-BrPA on aerobic glycolysis and kidney fibrosis in a unilateral ureteral obstruction (UUO) mice model and transforming growth factor-β1(TGF-β1)-stimulated normal rat kidney fibroblast (NRK49F) cell model in vitro.

Main Methods: In vivo UUO mouse model and in vitro TGF-β1 stimulated cell model were built. Immunohistochemical staining, Western blots, Real-time PCR and fluorescence microscopy were employed to detect extra cellular matrix (ECM) synthesis, fibroblast activation, aerobic glycolysis switch and related signaling pathways.

Key Findings: HE and Masson's Trichrome staining showed that 3-BrPA substantially suppressed kidney injury and interstitial collagen production. 3-BrPA also attenuated ECM accumulation in a dose-dependent manner, as shown by immunohistochemistry staining, RT-PCR and western blot. Furthermore, 3-BrPA inhibited FMT, as indicated by α-SMA and PCNA immunofluorescence double staining. Additionally, the results of MTT assay indicated 3-BrPA prevented TGF-β1 induced fibroblasts proliferation in a time- and dose-dependent manner. Mechanistically, molecular docking results showed that 3-BrPA effectively decreased the aerobic glycolysis related enzymes Hexokinase-2 (HK-2), Lactate dehydrogenase A (LDHA) and Pyruvate kinase isozymes M2 (PKM-2), as well as inhibited IL-1 receptor-associated kinase 4 (IRAK4)/MYC protein levels.

Significance: Our study highlighted that 3-BrPA is a potential reno-protective agent in kidney fibrosis through the inhibition of fibroblasts aerobic glycolysis might via IRAK4/MYC signal pathways.
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http://dx.doi.org/10.1016/j.lfs.2021.119206DOI Listing
May 2021

Immunological alterations in patients with chronic prostatitis/chronic pelvic pain syndrome and experimental autoimmune prostatitis model: A systematic review and meta-analysis.

Cytokine 2021 05 4;141:155440. Epub 2021 Feb 4.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei 230022, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei 230022, Anhui, PR China. Electronic address:

Background: As one of the most common conditions in urological outpatients, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) puzzles many individuals because of its unclear etiology and lack of effective treatment. Recently, immunological alterations underpinning CP/CPPS have been extensively investigated.

Methods: The PubMed, Web of Science, Cochrane library, and EMBASE databases were used to search original articles on immune mediators in patients with CP/CPPS and in experimental autoimmune prostatitis (EAP) models through April 10, 2020. Standardized mean differences (SMD) were calculated to summarize the differences in immune mediator levels between groups. Funnel plot, Begg's funnel plot, Egger's regression test, and the sensitivity analysis were applied to determine and visualize the stability of our findings.

Results: A total of 34 original studies were included in the meta-analysis, including 24 studies on patients with CP/CPPS and 10 studies on EAP models. We found that TNF-α, IL-1β, IL-6, and IL-8 were the four immune mediators that elevated in most of the samples derived from patients with CP/CPPS and the EAP models. The adjusted publication bias analysis indicated that publication bias was not existed, and the sensitivity analyses showed that the results were stable.

Conclusions: Immune responses play significant roles during the pathogenesis of CP/CPPS by promoting intraprostatic inflammation. Our findings provide potential diagnostic and therapeutic targets for CP/CPPS patients.
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http://dx.doi.org/10.1016/j.cyto.2021.155440DOI Listing
May 2021

Extracorporeal shock wave therapy decreases the number of total and degranulated mast cells and alleviates pelvic pain in a rat model of prostatitis.

Mol Cell Biochem 2021 Apr 25;476(4):1905-1913. Epub 2021 Jan 25.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease characterized by chronic pelvic pain. Extracorporeal shock wave therapy (ESWT) has been used to treat patients with CP/CPPS, but the parameters used by ESWT are not uniformly determined. Herein, this study aims to assess the effects of ESWT with different energy flux densities on pelvic pain in CP/CPPS rats and to explore the mechanisms. A rat model of CP/CPPS was induced by intraprostatic injection of 1% carrageenan. ESWT with different energy flux densities (0.09, 0.20, 0.30, 0.40 mJ/mm) was applied in the pelvic region of CP/CPPS rats once a week for 4 weeks. The results showed that compared with the other energy flux densities (0.09, 0.30, and 0.40 mJ/mm), ESWT with 0.20 mJ/mm exhibited a more powerful effect in alleviating pelvic pain and prostate damage. The therapeutic effect is associated with the reduction of the number of total and degranulated mast cells. Collectively, ESWT with 0.20 mJ/mm achieved the optimal therapeutic effect in alleviating pelvic pain in CP/CPPS rats.
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http://dx.doi.org/10.1007/s11010-020-04009-wDOI Listing
April 2021

Fifteen-MiRNA-Based Signature Is a Reliable Prognosis-Predicting Tool for Prostate Cancer Patients.

Int J Med Sci 2021 1;18(1):284-294. Epub 2021 Jan 1.

Department of Urology, The First Affiliated Hospital of Anhui Medical University and Institute of Urology and Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Jixi Road 218th, Shushan District, Hefei, Anhui, 230022, People's Republic of China.

Recurrence is a major problem for prostate cancer patients, thus, identifying prognosis-related markers to evaluate clinical outcomes is essential. Here, we established a fifteen-miRNA-based recurrence-free survival (RFS) predicting signature based on the miRNA expression profile extracted from The Cancer Genome Atlas (TCGA) database by the LASSO Cox regression analysis. The median risk score generated by the signature in both the TCGA training and the external Memorial Sloan-Kettering Cancer Center (MSKCC) validation cohorts was employed and the patients were subclassified into low- and high-risk subgroups. The Kaplan-Meier plot and log-rank analyses showed significant survival differences between low- and high-risk subgroups of patients (TCGA, log-rank < 0.001 & MSKCC, log-rank = 0.045). In addition, the receiver operating characteristic curves of both the training and external validation cohorts indicated the good performance of our model. After predicting the downstream genes of these miRNAs, the miRNA-mRNA network was visualized by Cytoscape software. In addition, pathway analyses found that the differences between two groups were mainly enriched on tumor progression and drug resistance-related pathways. Multivariate analyses revealed that the miRNA signature is an independent indicator of RFS prognosis for prostate cancer patients with or without clinicopathological features. In summary, our novel fifteen-miRNA-based prediction signature is a reliable method to evaluate the prognosis of prostate cancer patients.
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http://dx.doi.org/10.7150/ijms.49412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738977PMC
September 2021

Immune response drives outcomes in prostate cancer: implications for immunotherapy.

Mol Oncol 2021 May 29;15(5):1358-1375. Epub 2020 Dec 29.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

The heterogeneity of the immune microenvironment leads to different responses in immune checkpoint blockade therapy. We aimed to propose a robust molecular classification system to investigate the relevance of the immune microenvironment subtype and prognosis of prostate cancer patients, as well as the therapeutic response to immune checkpoint blockade therapy. A total of 1,557 prostate cancer patients were enrolled, including 69 real-world samples from our institute (titled the AHMU-PC cohort). The non-negative matrix factorization algorithm was employed to virtually microdissect patients. The immune enrichment was characterized by a high enrichment of T cell-, B cell-, NK cell-, and macrophage-associated signatures, by which patients were subclassified into nonimmune and immune classes. Subsequently, the immune class was dichotomized into immune-activated and immune-suppressed subtypes based on the stromal signature, represented by the activation of WNT/TGF-β, TGF-β1, and C-ECM signatures. Approximately 14.9% to 24.3% of patients belonged to the immune-activated subtype, which was associated with favorable recurrence-free survival outcomes. In addition, patients in the immune-activated subtype were predicted to benefit more from anti-PD-1/PD-L1 therapy. In conclusion, our study identifies a novel immune molecular classifier that is closely related to clinical prognosis and provides novel insights into immunotherapeutic strategies for prostate cancer patients.
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http://dx.doi.org/10.1002/1878-0261.12887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096785PMC
May 2021

Development of Mobile Application for Dynamically Monitoring the Risk of Prostate Cancer and Clinicopathology.

Cancer Manag Res 2020 26;12:12175-12184. Epub 2020 Nov 26.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.

Objective: To develop an application dynamically monitoring the prostate cancer (PCa) risk for patients to assess their own progression of PCa risk at home.

Methods: Between January 2010 and December 2019, all of the 1697 patients underwent transrectal ultrasound prostate biopsy at the cancer center, which is one of the Chinese Prostate Cancer Consortium. Patients' clinical parameters from January 2010 to May 2018 were used to establish models that consisted of several risk factors with P value <0.1 in univariate analysis and with P value <0.05 in multivariate analysis (n=1113), including model 1 (predicting PCa), model 2 (predicting PCa with high Gleason scores (7 or higher)) and model 3 (predicting PCa with the high clinical stage (T2b or higher)). Other patients from June 2018 to December 2019 were used to validate models (n=440). Patients with a lack of sufficient data were eventually excluded (n=144).

Results: A total of 1553 patients were involved in this study, and an application was used to perform the models. The predictive cut-off value and area under the curves (AUCs) of model 1, 2 and 3 were, respectively, calculated (cut-off: 0.53, 0.38 and 0.40, AUCs: 0.88, 0.89 and 0.89). Using a cut-off value of 10%, three models obtained a high sensitivity (>95%). Besides, more patients can be correctly reclassified via our models (42.9 to 55.5%). Decision curve analyses revealed a decent net benefit in any probability for models. These results were well verified in the validation cohort.

Conclusion: This application showed decent performance in predicting the risk of PCa and clinicopathology, which was available and convenient for patients to self-assess the progress of PCa risks so that being better to participate in disease management.
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http://dx.doi.org/10.2147/CMAR.S269783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705279PMC
November 2020

Marital Status and Prognostic Nomogram for Bladder Cancer With Distant Metastasis: A SEER-Based Study.

Front Oncol 2020 27;10:586458. Epub 2020 Oct 27.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology and Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.

Background: To investigate the impact of marital status on overall survival (OS) and create a prognostic nomogram predicting OS in distant-metastatic bladder cancer (DMBC) patients.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database was explored to recruit DMBC patients from 2010 to 2015. Kaplan-Meier survival analysis was used to compare survival differences among different marital status. Univariate and multivariate analyses were used to screen for prognostic factors and then constructed the nomogram based on Cox proportional hazard regression models. Calibration plot diagrams and concordance index (C-index) were used to verify the prognostic nomogram.

Results: Kaplan-Meier curves suggested the significant differences of OS among different marital status existed in total ( < 0.001), female ( = 0.011) and male ( = 0.001) DMBC patients, respectively. Multivariate analysis indicated marital status was an independent prognostic factor for OS of DMBC patients. Nomogram showed the contribution of marital status to predicting OS was small. Other independent prognostic factors included age, grade, histology type, surgery of primary site, chemotherapy, and metastasis pattern. By combining seven factors, we constructed a prognostic nomogram for DMBC patients. The C-index of this nomogram for OS prediction was 0.722 (95% CI 0.712-0.732). The calibration curves showed perfect consistency between observed and predictive survival.

Conclusions: Marital status was an independent prognostic factor for OS of DMBC patients, but its contribution to predicting OS was small. The prognostic nomogram will provide an individualized evaluation of OS and guidance for suitable treatments in DMBC patients.
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http://dx.doi.org/10.3389/fonc.2020.586458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654226PMC
October 2020

Comparative Efficacy of Combined Radiotherapy, Systemic Therapy, and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer: A Network Meta-Analysis and Systematic Review.

Front Oncol 2020 20;10:567616. Epub 2020 Oct 20.

Key Laboratory of Urological Diseases in Gansu Province, Department of Urology, Gansu Nephro-Urological Clinical Center, Lanzhou University Second Hospital, Lanzhou, China.

Recent randomized clinical trials have examined the efficacy of different combinations of systemic and local treatment approaches for metastatic hormone-sensitive prostate cancer (mHSPC). We compared the efficacy of these combined regimens in order to identify the optimal therapy for specific patient subgroups. The treatments were abiraterone (ABI), apalutamide (APA), docetaxel (DOC), enzalutamide (ENZ), and radiotherapy (RT) combined with androgen-deprivation therapy (ADT). Five electronic databases were searched up to May 7, 2020 for relevant trials. The risk of bias in the included trials was evaluated with the Cochrane tool. The hazard ratio (HR) with 95% confidence interval (CI) was determined for the included trials and indirect comparisons were performed using the R software. In total, 10 randomized, controlled trials with 11,194 patients were included in the meta-analysis. ADT + RT was superior to ADT monotherapy in terms of overall survival (HR = 0.96, 95% CI: 0.85-1.1) and conferred a survival benefit in a subgroup of low-volume patients (HR = 0.68, 95% CI: 0.54-0.87). Combined systemic treatments were significantly superior to ADT monotherapy in comparisons of survival and prostate-specific antigen response, including in the high-volume subgroup; meanwhile, in the low-volume subgroup only ADT + ENZ (HR = 0.38, 95% CI 0.21-0.69) showed a significant clinical benefit. In the Gleason score <8 subgroup, all combined systemic treatments were superior to ADT monotherapy, but the results were only significant for ADT + APA (HR = 0.56, 95% CI: 0.33-0.95) and ADT + DOC (HR = 0.71, 95% CI: 0.54-0.92). In the Gleason score ≥8 subgroup, ADT monotherapy was inferior (albeit not significantly) to combined treatments. In a ranking of performed comparisons, ADT + ENZ was the optimal regimen, although this was non-significant. Combined therapies also demonstrated superiority in quality-of-life indicators such as time to skeletal events and pain progression. ADT + radiotherapy led to superior outcomes in mHSPC patients with low-volume disease. While all combined systemic regimens confer a survival advantage over ADT monotherapy, the optimal treatment approach for certain mHSPC patient subgroups remains to be determined.
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http://dx.doi.org/10.3389/fonc.2020.567616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606969PMC
October 2020

Effects of RNA Binding Proteins on the Prognosis and Malignant Progression in Prostate Cancer.

Front Genet 2020 20;11:591667. Epub 2020 Oct 20.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Prostate cancer (PCa) is a common lethal malignancy in men. RNA binding proteins (RBPs) have been proven to regulate the biological processes of various tumors, but their roles in PCa remain less defined. In the present study, we used bioinformatics analysis to identify RBP genes with prognostic and diagnostic values. A total of 59 differentially expressed RBPs in PCa were obtained, comprising 28 upregulated and 31 downregulated RBP genes, which may play important roles in PCa. Functional enrichment analyses showed that these RBPs were mainly involved in mRNA processing, RNA splicing, and regulation of RNA splicing. Additionally, we identified nine RBP genes (EXO1, PABPC1L, REXO2, MBNL2, MSI1, CTU1, MAEL, YBX2, and ESRP2) and their prognostic values by a protein-protein interaction network and Cox regression analyses. The expression of these nine RBPs was validated using immunohistochemical staining between the tumor and normal samples. Further, the associations between the expression of these nine RBPs and pathological T staging, Gleason score, and lymph node metastasis were evaluated. Moreover, these nine RBP genes showed good diagnostic values and could categorize the PCa patients into two clusters with different malignant phenotypes. Finally, we constructed a prognostic model based on these nine RBP genes and validated them using three external datasets. The model showed good efficiency in predicting patient survival and was independent of other clinical factors. Therefore, our model could be used as a supplement for clinical factors to predict patient prognosis and thereby improve patient survival.
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http://dx.doi.org/10.3389/fgene.2020.591667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606971PMC
October 2020
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