Publications by authors named "Zuwei Li"

27 Publications

  • Page 1 of 1

m6A-Related lncRNA to Develop Prognostic Signature and Predict the Immune Landscape in Bladder Cancer.

J Oncol 2021 24;2021:7488188. Epub 2021 Jul 24.

Department of Pharmacy, Gaozhou People's Hospital, Maoming 525200, China.

Abnormal m6A methylation plays a significant role in cancer progression. Increasingly, researchers have focused on developing lncRNA signatures to evaluate the prognosis of cancer patients. The specific function of m6A-related lncRNAs in the prognosis of bladder cancer patients and the immune microenvironment of bladder cancer remains elusive. Herein, we performed a comprehensive analysis of m6A-related lncRNA prognostic values and their association with the immune microenvironment in bladder cancer using the TCGA dataset. A total of 9 m6A-related lncRNAs were dramatically correlated with overall survival outcomes in bladder cancer. Two molecular subtypes (cluster 1 and cluster 2) were identified by consensus clustering for 9 m6A-related prognostic lncRNAs. Cluster 1 was significantly correlated with poor prognosis, advanced clinical stage, higher PD-L1 expression, a higher ESTIMATEScore and immuneScore, and distinct immune cell infiltration. GSEA revealed the enrichment of apoptosis and the JAK-STAT signaling pathway in cluster 2. A prognostic risk score was constructed using 9 m6A-related prognostic lncRNAs, which functioned as an independent prognostic factor for bladder cancer. Moreover, bladder cancer patients in the low-risk score group had a higher pN stage, pT stage, and clinical stage and a lower tumor grade and immuneScore. The risk score was correlated with the infiltration levels of certain immune cells, including B cells, plasma cells, follicular helper T cells, regulatory T cells, resting NK cells, neutrophils, M0 macrophages, M1 macrophages, and M2 macrophages. Collectively, our study elucidated the important role of m6A-related lncRNAs in the prognosis of bladder cancer patients and in the bladder cancer immune microenvironment. The results suggest that the components of the m6A-related prognostic lncRNA signature might serve as a crucial mediator of the immune microenvironment in bladder cancer, representing promising therapeutic targets for improving immunotherapeutic efficacy.
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http://dx.doi.org/10.1155/2021/7488188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328735PMC
July 2021

Identification of the pyroptosis‑related prognostic gene signature and the associated regulation axis in lung adenocarcinoma.

Cell Death Discov 2021 Jun 25;7(1):161. Epub 2021 Jun 25.

Department of thoracic surgery, Gaozhou people's hospital, Gaozhou, 525200, China.

Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. Pyroptosis could regulate tumour cell proliferation, invasion, and metastasis, thereby affecting the prognosis of cancer patients. However, the role of pyroptosis-related genes (PRGs) in LUAD remains unclear. In our study, comprehensive bioinformatics analysis was performed to construct a prognostic gene model and ceRNA network. The correlations between PRGs and tumour-immune infiltration, tumour mutation burden, and microsatellite instability were evaluated using Pearson's correlation analysis. A total of 23 PRGs were upregulated or downregulated in LUAD. The genetic mutation variation landscape of PRG in LUAD was also summarised. Functional enrichment analysis revealed that these 33 PRGs were mainly involved in pyroptosis, the NOD-like receptor signalling pathway, and the Toll-like receptor signalling pathway. Prognosis analysis indicated a poor survival rate in LUAD patients with low expression of NLRP7, NLRP1, NLRP2, and NOD1 and high CASP6 expression. A prognostic PRG model constructed using the above five prognostic genes could predict the overall survival of LUAD patients with medium-to-high accuracy. Significant correlation was observed between prognostic PRGs and immune-cell infiltration, tumour mutation burden, and microsatellite instability. A ceRNA network was constructed to identify a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis in LUAD. In conclusion, we performed a comprehensive bioinformatics analysis and identified a prognostic PRG signature containing five genes (NLRP7, NLRP1, NLRP2, NOD1, and CASP6) for LUAD patients. Our results also identified a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis, which may also play an important role in the progression of LUAD. Further study needs to be conducted to verify this result.
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http://dx.doi.org/10.1038/s41420-021-00557-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257680PMC
June 2021

Teratogenic effects of environmentally relevant concentrations of phenanthrene on the early development of marine medaka (Oryzia melastigma).

Chemosphere 2020 Sep 25;254:126900. Epub 2020 Apr 25.

College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants in marine environments and have arouse great concern since they pose adverse effects to marine ecosystem. To determine the potential impacts of environmentally relevant PAHs on early life stages of marine fish, this study exposed embryos of marine medaka (Oryzias melastigma) to 0, 2, 10, 50, and 250 μg/L of phenanthrene (Phe), one of the most abundant PAHs. The results demonstrated that Phe exposure decreased hatching rates, delayed hatching time of embryos, and increased deformity rate of newly-hatched larvae. Exposure to 10 and 50 μg/L Phe decreased the survival rate of marine medaka larvae at 28 days post-fertilization (dpf), and no embryo successfully hatched in 250 μg/L Phe exposure group. Morphology results showed that 10, 50, and 250 μg/L Phe exposure significantly retarded the development of embryos, and 2, 10, and 50 μg/L caused yolk sac edema and pericardial edema in newly-hatched larvae, indicating that low concentrations of Phe could induce developmental cardiac toxicity. Furthermore, the changes in the expression of heart development-related genes were determined, and the results showed that Phe-induced cardiac malformation might be related with fgf8, bmp4, smyd1, ATPase and gata4 genes. Overall, environmentally relevant PAHs could disrupt heart morphogenesis and hatching process of marine medaka, which might have profound consequences for sustainability of fish population.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126900DOI Listing
September 2020

Tumor suppressor miR-33b-5p regulates cellular function and acts a prognostic biomarker in RCC.

Am J Transl Res 2020 15;12(7):3346-3360. Epub 2020 Jul 15.

Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital Shenzhen 518036, Guangdong, P. R. China.

Background: Renal cell carcinoma (RCC) is a renal parenchyma neoplasm with a 30% recurrence rate even when treated properly. MicroRNAs are noncoding small RNAs that are involved in cellular communication and may participate in cancer development. This study aimed to explore the relationship between miR-33b-5p expression and RCC progression and prognosis.

Method: RT-qPCR, CCK-8 assay, wound scratch assay, transwell assay and flow cytometry assay were used to evaluate the expression and function of miR-33b-5p in RCC. Additionally, RCC samples and survival data from The Cancer Genome Atlas were used to analyze the prognostic functions of miR-33b-5p.

Results: miR-33b-5p expression in RCC tissues and cell lines (786-O, ACHN) were found to be significantly downregulated, compared with normal tissues and cell lines (P<0.001). The miR-33b-5p mimic transfected cells showed a slower proliferation rate (P<0.01), while its invasion ability decreased by 38.16% (786-O, P<0.001) and 49.19% (ACHN, P<0.05), compared with the negative control (NC). The migration ability of both RCC lines were found to be as follows: miR-33b-5p inhibitor > NC or NC inhibitor > miR-33b-5p mimic. Additionally, TCGA and RCC samples reveal that low miR-33b-5p expression is related to poor survival outcomes (univariate analysis, P=0.029; multivariate analysis, P=0.024; Kaplan-Meier survival curves, P=0.014). Target genes prediction suggests that miR-33b-5p performs its tumor-suppressive effects and prognostic role through targeting TBX15, SLC12A5, and PTGFRN.

Conclusions: miR-33b-5p may function as a tumor-suppressive regulator and prognostic biomarker in RCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407706PMC
July 2020

Circadian clock is associated with tumor microenvironment in kidney renal clear cell carcinoma.

Aging (Albany NY) 2020 07 18;12(14):14620-14632. Epub 2020 Jul 18.

Department of Ophthalmology, Shantou University Medical College, Shantou 515041, China.

Background: Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent malignancies with high incidence and mortality. The circadian clock, which is also involved in the regulation of the immune system and tumor microenvironment, is an internal timing system that allows organisms to adjust biological processes and behaviors according to geophysical time.

Result: A wide range of circadian clock genes are epigenetically altered in KIRC, and associated with the overall survival and disease-free survival of patients. SNV analysis revealed missense mutation and splice site to be the most common variant types of circadian clock genes in KIRC. Several circadian clock genes were involved in the regulation of some cancer-related hallmark pathways, including apoptosis and cell cycle pathway. Further, immune infiltrates analysis not only revealed that the expression of circadian clock genes is associated with immune cell infiltrates, but also that somatic copy-number alteration of circadian clock genes could inhibit the immune infiltrates. Moreover, enrichment analysis implied that the circadian clock genes could regulate transcription factor activity and circadian rhythm in KIRC.

Conclusion: Our results demonstrate the potential of chrono-immunotherapy as a candidate option for the management of KIRC.

Method: Multi-omics analysis was performed to comprehensively determine the roles of core circadian clock genes in KIRC.
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http://dx.doi.org/10.18632/aging.103509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425457PMC
July 2020

Mining therapeutic and prognostic significance of STATs in renal cell carcinoma with bioinformatics analysis.

Genomics 2020 11 5;112(6):4100-4114. Epub 2020 Jul 5.

Department of Ophthalmology, Shantou University Medical college, Shantou 515041, China.

Renal cell carcinoma is one of the most common malignancies with high morbidity and mortality. STAT proteins play a significant role in cell biological behavior and immune response associated with cancer progression. In our study, the datasets analyzed for the expression and potential functions can be found in several bioinformatics analysis tools. We found that STAT1/2/4/6 were upregulated in RCC while STAT3/5B were downregulated. The expression of STAT2/4/5B were significantly associated with the pathological stage of RCC patients. RCC patients with high expression of STAT2/4 and low/medium expression of STAT5B had a poor overall survival. The function of STATs and the neighboring genes mainly enriched in JAK-STAT signaling pathway and NOD-like receptor signaling pathway. Several transcription factor, kinase, and miRNA targets were identified. Close correlations were obtained between immune cell infiltration and STATs in RCC. Our results have provided novel insights for the selection of immunotherapeutic targets and prognostic biomarkers.
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http://dx.doi.org/10.1016/j.ygeno.2020.06.032DOI Listing
November 2020

JAK3 is a potential biomarker and associated with immune infiltration in kidney renal clear cell carcinoma.

Int Immunopharmacol 2020 Sep 20;86:106706. Epub 2020 Jun 20.

Department of Pharmacy, Jiaying University Medical College, Meizhou 514015, China.

Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers globally, with an overall poor prognosis. The Janus kinase (JAK) family plays an essential role in cellular mechanisms such as proliferation, metastasis, invasion, and immunity. In our study, various web-portals were used to explore the expression and clinical significance of JAK3 in KIRC. JAK3 expression was significantly up-regulated in KIRC tissues. Patients with KIRC having high JAK3 levels displayed a substantially decreased disease-free survival rate and overall survival rate. Significant correlations were obtained between JAK3 expression and the abundance of immune cells and immune biomarker sets. Enrichment function analysis revealed that gene function significantly correlated with JAK3, which was primarily associated with the immune response, JAK-STAT signaling pathway, Ras signaling pathway via several cancer-related kinases, miRNAs, and transcription factors. Moreover, we also identified several kinase, miRNA or transcription factor targets of JAK3 in KIRC. The hub genes (JAK3, FCHO1, INSl3, DEF6, and GPR132) were associated with the activation or inhibition of several famous cancer related pathways. Our results demonstrated that JAK3 is a potential biomarker and associated with immune infiltration in KIRC.
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http://dx.doi.org/10.1016/j.intimp.2020.106706DOI Listing
September 2020

Identification of Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in the Renal Cell Carcinoma Microenvironment.

Front Oncol 2019 5;9:1555. Epub 2020 Feb 5.

Department of Hepatology, Gaozhou People's Hospital, Maoming, China.

Renal cell carcinoma (RCC) is one of the most common malignances with an ever-increasing incidence and high mortality. Cross-talk between cancer cells and interstitial cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. CXC chemokines in the tumor microenvironment can modulate immune cell trafficking and regulate tumor cell activities, thus exerting anti-tumor immunological effects and affecting patient outcomes; however, the expression and prognostic values of CXC chemokines in RCC have not been clarified. ONCOMINE, GEPIA, UALCAN, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TRRUST, LinkedOmics, and TIMER were utilized in this study. The transcriptional levels of in RCC tissues were significantly elevated while the transcriptional levels of CXCL3/7/12/13 were significantly reduced. A significant correlation was found between the expression of and the pathological stage of RCC patients. RCC patients with low transcriptional levels of were associated with a significantly better prognosis. The functions of differentially expressed CXC chemokines are primarily related to the chemokine signaling pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that RELA, NFKB1, and SP1 are key transcription factors for CXC chemokines, and the SRC family of tyrosine kinases (LCK, LYN, and FYN), mitogen-activated protein kinases (MAPK1 and MAPK3), and CSNK1D are CXC chemokine targets. We found significant correlations among the expression of CXC chemokines and the infiltration of six types of immune cells (B cells, CD8 T cells, CD4 T cells, macrophages, neutrophils, and dendritic cells). Our results may provide novel insights for the selection of immunotherapeutic targets and prognostic biomarkers for renal cell carcinoma.
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http://dx.doi.org/10.3389/fonc.2019.01555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012904PMC
February 2020

Bioinformatic identification of renal cell carcinoma microenvironment-associated biomarkers with therapeutic and prognostic value.

Life Sci 2020 Feb 8;243:117273. Epub 2020 Jan 8.

Department of Urology, Gaozhou People's Hospital, Maoming 525200, China. Electronic address:

Renal cell carcinoma (RCC) is the ninth most prevalent form of malignancy worldwide. The tumor microenvironment significantly affects gene expression in tumor tissues, which subsequently impacts the prognosis of RCC patients. Available datasets such as The Cancer Genome Atlas (TCGA) can be utilized to improve diagnostic methods and search for novel tumor therapeutic targets and prognostic biomarkers. The current study used the ESTIMATE algorithm to explore the immune and stromal components in RCC. Differentially expressed genes (DEGs) were identified by comparing the gene expression patterns in groups with high and low immune/stromal scores. Functional enrichment analysis was conducted and Kaplan-Meier survival curves were plotted to explore the functions of the DEGs in the tumorigenesis, progression, and prognosis of RCC. Our results revealed that immune and stromal scores are associated with specific clinicopathologic variables in RCC. These variables include gender, tumor grade, tumor stage, tumor size, distant metastasis and prognosis. A total of 48 upregulated and 47 downregulated genes were obtained. Functional enrichment analysis demonstrated a correlation between DEGs and the tumor microenvironment, tumor immune response and RCC tumorigenesis. Kaplan-Meier survival curves showed that 43 out of the 48 identified tumor microenvironment related genes are involved in the prognosis of RCC. Three genes, IL10, IGLL5 and POU2AF1, were selected as the hub genes, and their kinase targets were identified as MAPK1 and PPKCA. A positive correlation was obtained between the expression of IL/POU2AF1 and the abundance of six immune cells. Our study provides potential biomarkers for the therapy and prognosis of RCC.
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http://dx.doi.org/10.1016/j.lfs.2020.117273DOI Listing
February 2020

miR-625-3p promotes migration and invasion and reduces apoptosis of clear cell renal cell carcinoma.

Am J Transl Res 2019 15;11(10):6475-6486. Epub 2019 Oct 15.

Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University Shenzhen 518036, Guangdong, P. R. China.

Clear cell renal cell carcinoma (ccRCC) is a common malignancy, yet, the mechanisms underlying tumorigenesis remain unclear. Several miRNAs have been implicated in the development of RCC previously via regulation of target gene expression. As miR-625-3p has recently been identified to play a role in development of other malignancies and is reportedly upregulated in ccRCC, we sought to investigate the role of this miRNA in the progression of ccRCC. Analysis of 30 paired fresh ccRCC tissues and adjacent normal renal tissues revealed that the expression of miR-625-3p was increased in ccRCC tissues compared to normal tissues. Subsequently, in 136 formalin-fixed paraffin-embedded ccRCC tissues, the increased miR-625-3p expression was correlated with poor prognosis for ccRCC patients. The diagnostic value of miR-625-3p was identified in 50 ccRCC patients and 74 healthy controls by ROC curve. miR-625-3p was decreased in serum of ccRCC patients compared to healthy individuals. miR-625-3p could serve as a promising serum biomarker for yielding an area under the receiver operating characteristic curve of 0.792 with 70.3% sensitivity and 80.0% specificity in discriminating ccRCC from healthy individuals. Using in vitro functional assays, we found that overexpression of miR-625-3p promoted migration and invasion of ccRCC cells but reduced ccRCC cell apoptosis. Inhibition of miR-625-3p, on the other hand, exerted the opposite effects. Bioinformatic analyses indicated that predicted gene targets of miR-625-3p are correlated with lower overall survival of ccRCC patients. Together, these findings demonstrate that miR-625-3p promotes ccRCC migration and invasion and reduces apoptosis, providing a prognostic marker for survival and a potential diagnostic and therapeutic target against ccRCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834509PMC
October 2019

Field-free spin-orbit-torque switching of perpendicular magnetization aided by uniaxial shape anisotropy.

Nanotechnology 2019 Sep 10;30(37):375202. Epub 2019 Jun 10.

School of Microelectronics, Beijing Advanced Innovation Center for Big Data and Brain Computing, Fert Beijing Research Institute, Beihang University, Beijing, 100191, People's Republic of China. Beihang-Goertek Joint Microelectronics Institute, Qingdao Research Institute, Beihang University, Qingdao 266100, People's Republic of China.

It has been demonstrated that the switching of perpendicular magnetization can be achieved with spin-orbit torque (SOT) at an ultrafast speed and low energy consumption. However, to make the switching deterministic, an undesirable magnetic field or unconventional device geometry is required to break the structure inverse symmetry. Here we propose a novel scheme for SOT-induced field-free deterministic switching of perpendicular magnetization. The proposed scheme can be implemented in a simple magnetic tunnel junction (MTJ)/heavy-metal system, without the need of complicated device structure. The perpendicular-anisotropy MTJ is patterned into elliptical shape and misaligned with the axis of the heavy metal, so that the uniaxial shape anisotropy aids the magnetization switching. Furthermore, unlike the conventional switching scheme where the switched final magnetization state is dependent on the direction of the applied current, in our scheme the bipolar switching is implemented by choosing different current paths, which offers a new freedom for developing novel spintronics memories or logic devices. Through the macrospin simulation, we show that a wide operation window of the applied current pulse can be obtained in the proposed scheme. The precise control of pulse amplitude or pulse duration is not required. The influences of key parameters such as damping constant and field-like torque strength are discussed as well.
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http://dx.doi.org/10.1088/1361-6528/ab2831DOI Listing
September 2019

MiR-378a-5p acts as a tumor suppressor in renal cell carcinoma and is associated with the good prognosis of patients.

Am J Transl Res 2019 15;11(4):2207-2218. Epub 2019 Apr 15.

Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University Shenzhen 518036, Guangdong, P. R. China.

Renal cell carcinoma (RCC) is a common cancer that accounts for about 1.6% of all malignancies. Accumulating evidence has shown that miRNAs may play important roles in the development of cancers and that these same miRNAs may serve as diagnostic and prognostic biomarkers. The role of the miRNA miR-378a-5p in RCC, however, has been largely unexplored. In our study, we have demonstrated that miR-378a-5p expression was decreased in renal tissues and in RCC cell lines compared with corresponding expression levels in normal renal tissues and in the 293-T cell line. Functional studies in two RCC cell lines (ACHN and 786-O) have indicated that miR-378a-5p overexpression attenuated cell proliferation, migration, and invasion while promoting cell apoptosis. Inhibition of miR-378a-5p expression, on the other hand, promoted cell proliferation, migration, and invasion while reducing cell apoptosis. Additionally, in 42 cases of renal cancer formalin-fixed paraffin-embedded specimens, patients with higher expression levels of miR-378a-5p had significantly longer overall survival rates (P<0.05) than patients with lower miR-378a-5p expression levels. Thus, in this study, we have shown that miR-378a-5p can serve as a tumor suppressor and a potential prognostic biomarker in RCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511777PMC
April 2019

Corrigendum to "MiR-23a-3p acts as an oncogene and potential prognostic biomarker by targeting PNRC2 in RCC" [Biomed. Pharmacother. 110 (2019) 656-666].

Biomed Pharmacother 2019 04 11;112:108755. Epub 2019 Mar 11.

Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, PR China; Clinical College, Peking University Shenzhen Hospital, Anhui Medical University, Hefei, Anhui, 230032, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.biopha.2019.108755DOI Listing
April 2019

Upregulation of miR-183-5p predicts worse survival in patients with renal cell cancer after surgery.

Cancer Biomark 2019 ;24(2):153-158

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China.

Objective: Renal cell carcinoma (RCC) is one of the most common genitourinary cancers, and advanced RCC usually leads to poor prognosis. Therefore, identifying novel biomarkers for predicting the progression and prognosis of RCC is essential. The present study aims to evaluate the clinical value of miR-183-5p in RCC development and prognosis after surgery.

Materials And Methods: We enrolled a total of 284 patients who received partial or radical nephrectomy from April 2003 to May 2013 at a single institution. The clinical and pathological characteristics of the patients were collected, including age, gender, tumor size, tumor stage, as well as follow-up information. The expression levels of miR-183-5p of all the patients were calculated from FFPE specimens. Cox regression analyses were performed to approve the effect of miR-183-5p expression on patient survival. Kaplan-Meier method was used to analyze the patient survival curves.

Results: After controlling for gender, age, tumor size and tumor stage in the multivariate analysis, we found that high expression of miR-183-5p was independently associated lower overall survival (HR = 0.550, 95% CI = 0.364-0.832, p= 0.005). The Kaplan-Meier analysis also showed that patients with high expression of miR-183-5p had a significantly poor prognosis (p= 0.006). These results was verified by analyzing the data of 506 cases from The Cancer Genome Atlas database (TCGA).

Conclusion: Our results indicated that the high miR-183-5p expression is an independent factor for predicting RCC's worse prognosis.
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http://dx.doi.org/10.3233/CBM-182047DOI Listing
July 2019

MiR-23a-3p acts as an oncogene and potential prognostic biomarker by targeting PNRC2 in RCC.

Biomed Pharmacother 2019 Feb 12;110:656-666. Epub 2018 Dec 12.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address:

Background: Renal cell carcinoma (RCC) is a most common kidney malignancy, with atypical symptoms in the early stage and poor outcome in the late stage. Recently, emerging evidence revealed that some miRNAs play an essential role in the tumorigenesis and progression of RCC. Therefore, the aim of this study is that understand the detailed molecular mechanism of miR-23a-3p in RCC and identify its potential clinical value.

Methods: In this study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay and flow cytometry assay were performed to detect miR-23a-3p expression and its proliferation, migration and apoptosis in RCC. The bioinformatics analysis, RT-qPCR, western blot and luciferase reporter assay were performed to discern and examine the relationship between miR-23a-3p and its potential targets. Moreover, we analyzed the relationship between miR-23a-3p expression and clinicopathological variables or overall survival (OS) from 118 formalin-fixed paraffin-embedded RCC samples.

Results: miR-23a-3p is significantly up-regulated in RCC tissue samples, RCC cell lines and the TCGA database. Upregulating miR-23a-3p enhances, while silencing miR-23a-3p suppresses cell viability, proliferation and mobility in ACHN and 786-O cell lines. Besides, overexpression of miR-23a-3p inhibits the cell apoptosis. Then our study further reveals that miR-23a-3p regulates tumorigenesis by targeting Proline-Rich Nuclear Receptor Coactivator 2 (PNRC2). Also, the cox proportional hazard regression analysis indicates that low expression of miR-23a-3p patients has a remarkable longer OS.

Conclusions: Our results reveals that miR-23a-3p may not only serve as a new biomarker for prognosis but also serve as a new therapeutic strategy in the RCC treatment.
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http://dx.doi.org/10.1016/j.biopha.2018.11.065DOI Listing
February 2019

LncRNA as a diagnostic and prognostic biomarker in bladder cancer: a systematic review and meta-analysis.

Onco Targets Ther 2018 4;11:6415-6424. Epub 2018 Oct 4.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China,

Background: Bladder cancer is one of the most common urinary malignancies, and has a high recurrence rate and poor outcomes. In order to identify novel diagnostic and prognostic biomarkers for bladder cancer, we conducted a meta-analysis to analyze the association between long non-coding RNA (lncRNA) expression and survival in bladder cancer.

Materials And Methods: We searched literature from databases using our inclusion and exclusion criteria. STATA 14.0 software was used to analyze the data from collected studies and to construct the forest plots. A different effect size was selected for each meta-analysis.

Results: After selection, 30 articles were found to be eligible. The present meta-analysis contains data from 13 articles about clinicopathological characteristics, six articles about diagnosis, and 16 articles about prognosis. In the present study, we found that many lncRNAs could function as potential diagnostic and prognostic markers in bladder cancer. Among these findings, UCA1 was expected to be a diagnostic biomarker for bladder cancer, while the aberrant expression of HOTAIR and GAS5 was associated with poor disease-free survival/recurrence-free survival/disease-specific survival.

Conclusion: Overall, the present study is the first meta-analysis to assess the association between expression of lncRNAs and clinical value in patients with bladder cancer. LncRNAs hold promise as novel diagnostic and prognostic markers in bladder cancer.
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http://dx.doi.org/10.2147/OTT.S167853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177400PMC
October 2018

MicroRNA‑222‑3p promotes tumor cell migration and invasion and inhibits apoptosis, and is correlated with an unfavorable prognosis of patients with renal cell carcinoma.

Int J Mol Med 2019 Jan 15;43(1):525-534. Epub 2018 Oct 15.

Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.

The aim of the present study was to investigate the role of microRNA (miR)‑222‑3p in renal cell carcinoma (RCC). The expression level of miR‑222‑3p was detected in RCC tissues and cell lines (ACHN, 786‑O, Caki‑1 and 769‑P) and was identified to be significantly upregulated compared with the level in adjacent normal renal tissues and HK‑2 cells. Further in vitro experiments demonstrated that the over-expression of miR‑222‑3p promoted the migration and invasion, and attenuated the apoptosis of 786‑O cells, whereas the knockdown of miR‑222‑3p suppressed the migration and invasion and induced the apoptosis of 786‑O cells. Similar results were observed in the ACHN cell line in terms of migration, invasion and apoptosis. Furthermore, the expression level of miR‑222‑3p was measured in 42 RCC formaldehyde‑fixed paraffin‑embedded samples, and the association between the expression of miR‑222‑3p and the pathological characteristics and overall survival rate of patients with RCC was analyzed. The results demonstrated that patients with a higher expression of miR‑222‑3p had a significantly lower overall survival rate, compared with those with a lower expression of miR‑222‑3p [hazard ratio (HR)=5.120; P=0.036]. Multivariate analysis identified that patients with a higher expression of miR‑222‑3p retained the statistically significant decrease in overall survival rate compared with patients with a lower expression of miR‑222‑3p (HR=5.636; P=0.030). Furthermore, Kaplan‑Meier survival curves indicated that patients with higher miR‑222‑3p had significantly lower overall survival rates compared with patients with lower miR‑222‑3p (P=0.020). Taken together, these results suggested that miR‑222‑3p serves as an onco‑miR in RCC and may be a potential prognostic biomarker and therapeutic target in patients with RCC.
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http://dx.doi.org/10.3892/ijmm.2018.3931DOI Listing
January 2019

Primary small-cell neuroendocrine carcinoma of the urinary bladder: A rare case and a review of the literature.

Mol Clin Oncol 2018 Sep 19;9(3):335-338. Epub 2018 Jul 19.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.

Primary small-cell neuroendocrine carcinoma (SCNEC) of the urinary bladder is a rare tumor characterized by poor differentiation and high aggressiveness. Only ~150 cases have been reported in the literature to date. We herein present a case of an 87-year-old man who presented with hematuria and was found to have an ill-defined mass in the urinary bladder on computed tomography and cystoscopic examination. On pathological examination following tumor biopsy, the mucosa of the bladder wall was found to be extensively infiltrated by neuroendocrine carcinoma, positive for CD56 and synaptophysin and negative for epithelial membrane antigen, consistent with SCNEC of the urinary bladder. The patient refused further surgical treatment and succumbed to the disease 2 months after the diagnosis. In the present study, this rare case of primary SCNEC of the urinary bladder is presented, along with a discussion on the clinical presentation, immunohistochemical and cytomorphological characteristics, management, biological behavior and prognosis of this disease.
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http://dx.doi.org/10.3892/mco.2018.1679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109670PMC
September 2018

Oncogene miR-154-5p regulates cellular function and acts as a molecular marker with poor prognosis in renal cell carcinoma.

Life Sci 2018 Sep 21;209:481-489. Epub 2018 Aug 21.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China. Electronic address:

Aims: In adult population, the renal cell carcinoma (RCC) is one of the most common urological malignancies. It is meaningful to research for the molecular markers which are involved in the occurrence and development of RCC. Therefore, we concentrate on illuminating the role of microRNA-154-5p in progression of RCC and explore its prognostic values.

Main Methods: The real-time quantitative polymerase chain reaction (RT-qPCR) was applied to determine expression level of miR-154-5p in tissues. Afterwards, the transfected cell lines ACHN and 786-O were used for the CCK-8 assay, MTT assay, wound healing assay, transwell assay and flow cytometric assay to explore the role of miR-154-5p in regulating cellular function. In addition, formalin-fixed paraffin-embedded (FFPE) renal cancer samples were used for detecting the relationship between expression level of miR-154-5p and clinical information. Furthermore, univariate and multivariate Cox proportional-hazards regression analyses, and the Kaplan-Meier survival curves were performed to evaluate the prognostic value of miR-154-5p in RCC.

Key Findings: The RT-qPCR indicated that miR-154-5p is up-regulated in RCC pathologic specimens and cell lines. Results of study also demonstrated that upregulation of miR-154-5p reduced cell apoptosis and promoted cell proliferation, viability, migration as well as invasion in RCC cells. The prognosis analyses indicated that the expression level of miR-154-5p is associated with the prognosis of renal cancer, and the overall survival of patients with low expression is longer.

Significance: The present study revealed that the oncogene miR-154-5p regulates cellular function and acts as a molecular marker with poor prognosis in renal cell carcinoma.
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http://dx.doi.org/10.1016/j.lfs.2018.08.044DOI Listing
September 2018

microRNA‑572 functions as an oncogene and a potential biomarker for renal cell carcinoma prognosis.

Oncol Rep 2018 Nov 17;40(5):3092-3101. Epub 2018 Aug 17.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.

Renal cell carcinoma (RCC) is the third most common urological malignancy in the USA and represents 2‑3% of all adult malignancies. Furthermore, the incidence of RCC has been progressively increasing over recent years. Although the morbidity of treatment has decreased with the use of multidisciplinary synthetic therapy, the prognosis of terminal cancer remains poor, with a 5‑year survival rate of 5‑10%. MicroRNAs (miRs) have been correlated with the regulation of 30‑60% of the protein-coding genes and act as oncogenes or anti‑oncogenes in RCC. Considering this research, miRNAs are likely to be the biomarkers for tumor diagnosis, prognosis and the targets for RCC management. In the present study, 42 formalin‑fixed paraffin‑embedded RCC samples were used. The expression of miR‑572 and the role of miR‑572 in RCC cell proliferation, migration and apoptosis was determined by performing reverse transcription‑quantitative polymerase chain reaction analysis, wound scratch assays, cell proliferation assays, Transwell assays and flow cytometry assays, respectively. Further experiments were conducted to clarify the correlation between miR‑572 expression and clinicopathological variables or overall survival. Furthermore, the expression levels of miR‑572 were evaluated for the prognosis value of patients with RCC. Upregulation of miR‑572 was observed in RCC tissues and RCC cell lines. miR‑572 promoted 786‑O and ACHN cell proliferation and mobility and inhibited early apoptosis. In Cox proportional hazard regression analyses, results of the univariate and multivariate analysis indicated that the patients with low miR‑572 expression had a significantly longer overall survival compared with the patients with high miR‑572 expression (univariate analysis, P=0.037; multivariate analysis, P=0.034). Results of the Kaplan‑Meier survival curves revealed that the patients with downregulated miR‑572 have a significantly longer overall survival compared with the patients with highly expressed miR‑572 (P=0.019). To conclude, the results of the present study suggest that tumor oncogene miR‑572 is a potential biomarker for the diagnosis, treatment and prognosis for RCC.
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http://dx.doi.org/10.3892/or.2018.6649DOI Listing
November 2018

Giant posterior pararenal schwannoma: A case report and review of literature.

Mol Clin Oncol 2018 Sep 3;9(3):325-328. Epub 2018 Jul 3.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.

Schwannomas, arising from Schwann cells of peripheral nerve sheaths, are primarily benign tumors. They are rarely found in the retroperitoneal space. To date, ~30 cases on giant retroperitoneal schwannomas have been reported. Those with a location of pararenal space are even rarer. Clinically, they are often misdiagnosed as malignancies. In the present study, a case of a 35-year-old woman with a giant schwannoma measuring 13 × 8.5 × 6.5 cm in the posterior pararenal space of left retroperitoneum was presented, which was thought to be a malignant tumor from the result of computed tomography scan. Later postoperative pathology and immunohistochemistry were consistent with benign schwannoma. To the best of our knowledge, this was the largest posterior pararenal schwannoma reported in literature. It is significant to report this case, and summarize the characteristics, diagnosis, treatment and prognosis of the similar cases. Furthermore, a brief review of the previously published cases in literature is provided.
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http://dx.doi.org/10.3892/mco.2018.1664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090574PMC
September 2018

MiR-302b regulates cell functions and acts as a potential biomarker to predict recurrence in bladder cancer.

Life Sci 2018 Sep 31;209:15-23. Epub 2018 Jul 31.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China. Electronic address:

Background: Bladder cancer is the most common urogenital tumor with substantial morbidity, high recurrence rate and mortality. miRNAs, a class of endogenous noncoding RNA, were found to involve in the genesis, maintenance and metastasis of cancer. Genomic profiling revealed that miR-302b is down-regulated in bladder cancer while its functions in bladder cancer remain to be ascertained.

Methods: Cell functional assays including wound healing assay, CCK-8 assay, Transwell assay and flow cytometry assay were performed to clarify the functions of miR-302b expression in cell proliferation, migration, invasion and apoptosis in BC. Furthermore, RT-qPCR was performed to study the expression of miR-302b in bladder cancer tissues and the prognostic value of altered miR-302b expression with 48 formalin-fixed paraffin-embedded bladder urothelial carcinoma samples.

Results: The results of RT-qPCR demonstrated that expression level of miR-302b was significantly reduced in bladder cancer tissues and cell lines. The cells after transfected with miR-302b mimic showed lower mobility, lower proliferation and increased apoptosis, while opposite results were obtained after inhibiting the expression of miR-302b. The prognosis analysis demonstrated that the patients with low expression of miR-302b experienced high risks of recurrence.

Conclusions: The results of our study demonstrate that miR-302b regulates cell functions and acts as a potential biomarker to predict recurrence in bladder cancer.
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http://dx.doi.org/10.1016/j.lfs.2018.07.057DOI Listing
September 2018

Oncogenic miR-663a is associated with cellular function and poor prognosis in renal cell carcinoma.

Biomed Pharmacother 2018 Sep 21;105:1155-1163. Epub 2018 Jun 21.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China. Electronic address:

Background: MicroRNA(miRNA) plays a key regulatory role in various stages of tumorigenesis, including cell growth, cell cycle control, apoptosis avoidance, tissue invasion, and metastasis. Several microRNAs are involved in the development of renal cell carcinoma (RCC) and the malignant transformation process. However, the effects of miR-663a on RCC have rarely been reported.

Methods: In the present study, the expression of miR-663a was examined in RCC using matched normal kidney tissues and four cell lines (786-O, Caki-1, ACHN and HK-2). MicroRNA mimics were transiently transfected into RCC cells and the effects of over expression on proliferation, migration, invasion, and apoptosis was observed. In addition, the relationship between miR-663a expression in 42 formalin-fixed paraffin-embedded (FFPE) clear cell renal carcinoma (ccRCC) samples and clinical pathological variables and overall survival was investigated. We evaluated the prognostic value of miR-663a expression in ccRCC by experimental results.

Results: The results showed that the expression of miR-663a was up-regulated in RCC cells and tissues and miR-663a was associated with proliferation, migration, invasion, and apoptosis of RCC. Cox proportional hazard regression analysis showed that a high expression of miR-663a patients had a significantly shorter overall survival in univariate and multivariate analysis. Kaplan-Meier survival curves showed that a high expression of miR-663a patients had a significantly shorter overall survival.

Conclusions: These results indicate that miR-663a can be used as an independent marker for the poor prognosis of ccRCC, and may also play an important role as a tumor oncogene in the occurrence and development of RCC.
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http://dx.doi.org/10.1016/j.biopha.2018.05.082DOI Listing
September 2018

Identification of miR-18a-5p as an oncogene and prognostic biomarker in RCC.

Am J Transl Res 2018 15;10(6):1874-1886. Epub 2018 Jun 15.

Department of Urology, Peking University Shenzhen Hospital Shenzhen 518036, Guangdong, China.

Background: RCC is a malignant tumor that originates from renal tubular epithelial cells, accounting for nearly 90% of renal malignancies and 3% of adult malignancies. It was reported that more than 30-40% of patients with early localized RCC still have recurrence and metastasis after receiving radical surgery. miRNAs are an endogenous non-coding small RNAs that play an important role in the regulation of tumor cell proliferation, differentiation and apoptosis.

Methods: In our study, RT-qPCR, CCK-8 assay, wound scratch assay, transwell assay and flow cytometry assay were designed to identify the expression and functions of miR-18a-5p in RCC. Moreover, we collected the survival data from The Cancer Genome Atlas to predict and clarify the prognostic functions of miR-18a-5p in RCC. The correlation between miR-18a-5p expression and clinicopathological variables or overall survival was analyzed by 42 formalin-fixed paraffin-embedded (FFPE) renal cancer samples.

Results: The expression of miR-18a-5p in RCC tissues and cell lines was elevated. Further researches suggested that upregulation of miR-18a-5p had a positive effect on RCC cell proliferation, migration, invasion and inhibition of apoptosis, while down-regulation of miR-18a-5p neutralized the effect. In addition, Data of TCGA and prognostic analysis of FFPE RCC samples revealed that high miR-18a-5p expression patients had significantly poorer survival.

Conclusions: These results demonstrated that miR-18a-5p functioned as an oncogene and prognostic biomarker in RCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038077PMC
June 2018

Oncogene miR-187-5p is associated with cellular proliferation, migration, invasion, apoptosis and an increased risk of recurrence in bladder cancer.

Biomed Pharmacother 2018 Sep 5;105:461-469. Epub 2018 Jun 5.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China. Electronic address:

Background: Bladder cancer, the ninth-most-common malignancy worldwide with an estimated 356,000 new cases and 145,000 deaths annually, has a propensity to relapse, requiring lifelong monitoring after diagnosis. 75% patients diagnosed with BC are non-muscle invasive BC and over 50% of them experience recurrences within 6-12 years of initial diagnosis. miRNA are small, noncoding RNA and shown to be oncogenes or anti-oncogenes in bladder cancer, contributing to numerous BC cell processes, including cell proliferation, differentiation, migration and apoptosis.

Methods: RT-qPCR were performed to detect the expression of miR-187-5p in tissues and cell lines, After which, clinicopathological variables and the prognostic value of altered miR-187-5p expression in BC was analyzed with the 48 formalin-fixed paraffin-embedded BC samples. Moreover, Cell functional assays (wound healing assay, CCK-8 assay, transwell assay and flow cytometry assay) were performed to explore the relationship between miR-187-5p expression and cell proliferation, migration, invasion and apoptosis in BC.

Results: Up-regulation of miR-187-5p was observed in BC tissues and BC cell lines. Cox proportional hazard regression analysis demonstrated that the patients with low expression of miR-187-5p experience lower risks of recurrence in the univariate and multivariate analysis. The Kaplan-Meier recurrence-free curves suggested that the patients with low expression of miR-187-5p experience lower risks of recurrence. Up-regulation of miR-187-5p promotes cell proliferation and mobility and inhibits the apoptosis of 5637 and UM-UC-3 cell, while down-regulation of miR-187-5p reverses these effects.

Conclusions: The results of our study demonstrated that oncogene miR-187-5p is associated with cellular proliferation, migration, invasion, apoptosis and an increased risk of recurrence in bladder cancer.
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http://dx.doi.org/10.1016/j.biopha.2018.05.122DOI Listing
September 2018

miR-566 functions as an oncogene and a potential biomarker for prognosis in renal cell carcinoma.

Biomed Pharmacother 2018 Jun 5;102:718-727. Epub 2018 Apr 5.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China. Electronic address:

Background: Renal cell carcinoma (RCC), a heterogeneous type of cancer originating from the nephron, occupies approximately 3.9% of new carcinomas, with an increasing incidence in the past two decades. The most common subtype of renal cell carcinoma is clear cell RCC (ccRCC). Though surgery and other treatments are applied to RCC, it has the highest recurrence rate and mortality rate among the genitourinary cancers. As the study progressed, miRNAs are found to be the biomarkers for tumor diagnosis, prognosis and the targets for tumor management.

Methods: In present study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay and flow cytometry assay were performed to ascertain miR-566 expression level and its proliferation, migration and apoptosis in RCC. Moreover, we analyzed the relation between miR-566 expression and clinicopathological variables or overall survival from the 42 formalin-fixed paraffin-embedded (FFPE) renal cancer samples. We further evaluate prognostic values of miR-566 expression.

Results: miR-566 is up-regulated in RCC tissue samples and renal carcinoma cell lines. miR-566 promotes cell proliferation, mobility and inhibits cell apoptosis in 786-O and ACHN cell lines. Cox proportional hazard regression analysis indicates that low expression of miR-566 patients have a remarkable longer overall survival in the univariate and multivariate analysis. The Kaplan-Meier survival curves show that the low expression of miR-566 patients have a remarkable longer overall survival.

Conclusions: The results of the current study demonstrate that oncogene miR-566 is a potential biomarker not only for diagnosis but also for prognosis for RCC.
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http://dx.doi.org/10.1016/j.biopha.2018.03.072DOI Listing
June 2018

Giant paratesticular liposarcoma: A case report and review of the literature.

Mol Clin Oncol 2018 04 15;8(4):613-616. Epub 2018 Feb 15.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen 518036, P.R. China.

Paratesticular liposarcoma is an infrequent tumor characterized by a growing, painless, inguinal or scrotal mass. Only about 200 cases have been reported as of yet in literature, however there are a few cases regarding giant paratesticular liposarcoma measuring over 10 cm. The disease may be commonly misdiagnosed prior to operation. Improper treatment tends to lead to local recurrence and distant metastasis. The current report presents a case of a 51-year-old patient with a large, painless right scrotum. Magnetic resonance imaging revealed a 7.8×5.8×10.4 cm nonhomogeneous space-occupying lesion of the right testis, which was firstly diagnosed as a spermatocytoma. Following this, a radical orchiectomy of the right testis was performed, however, it appeared to be a dedifferentiated liposarcoma, following histopathological examination and immunohistochemistry. Due to the large size of the tumor, it is significant to report the characteristics, diagnosis and treatment of the similar cases. The current study additionally presents a supplementary review of previously published cases in literature and focuses on discussion regarding the clinical characteristics, diagnosis, histopathology and immunohistochemical features and treatment of this disease.
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http://dx.doi.org/10.3892/mco.2018.1577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844082PMC
April 2018
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