Publications by authors named "Shaoxu Wu"

16 Publications

  • Page 1 of 1

An Artificial Intelligence System for the Detection of Bladder Cancer via Cystoscopy: A Multicenter Diagnostic Study.

J Natl Cancer Inst 2021 Sep 2. Epub 2021 Sep 2.

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Cystoscopy plays an important role in bladder cancer (BCa) diagnosis and treatment, but its sensitivity needs improvement. Artificial intelligence has shown promise in endoscopy, but few cystoscopic applications have been reported. We report a Cystoscopy Artificial Intelligence Diagnostic System (CAIDS) for BCa diagnosis.

Methods: In total, 69,204 images from 10,729 consecutive patients from six hospitals were collected and divided into training, internal validation, and external validation sets. The CAIDS was built using a pyramid scene parsing network and transfer learning. A subset (n = 260) of the validation sets was used for a performance comparison between the CAIDS and urologists for complex lesion detection. The diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values and 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method.

Results: The diagnostic accuracies of the CAIDS were 0.977 (95% CI = 0.974-0.979) in the internal validation set and 0.990 (95% CI = 0.979-0.996), 0.982 (95% CI = 0.974-0.988), 0.978 (95% CI = 0.959-0.989), and 0.991 (95% CI = 0.987-0.994) in different external validation sets. In the CAIDS versus urologists' comparisons, the CAIDS showed high accuracy and sensitivity (accuracy = 0.939, 95% CI = 0.902-0.964; and sensitivity = 0.954, 95% CI = 0.902-0.983) with a short latency of 12 s, much more accurate and quicker than the expert urologists.

Conclusions: The CAIDS achieved accurate BCa detection with a short latency. The CAIDS may provide many clinical benefits, from increasing the diagnostic accuracy for BCa, even for commonly misdiagnosed cases such as flat cancerous tissue (carcinoma in situ), to reducing the operation time for cystoscopy.
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http://dx.doi.org/10.1093/jnci/djab179DOI Listing
September 2021

A multicenter study to develop a non-invasive radiomic model to identify urinary infection stone in vivo using machine-learning.

Kidney Int 2021 Jun 12. Epub 2021 Jun 12.

Department of Pharmacy, the First People's Hospital of Kashi Prefecture, Affiliated Kashi Hospital of Sun Yat-Sen University, Kashi, People's Republic of China. Electronic address:

Urolithiasis is a common urological disease, and treatment strategy options vary between different stone types. However, accurate detection of stone composition can only be performed in vitro. The management of infection stones is particularly challenging with yet no effective approach to pre-operatively identify infection stones from non-infection stones. Therefore, we aimed to develop a radiomic model for preoperatively identifying infection stones with multicenter validation. In total, 1198 eligible patients with urolithiasis from three centers were divided into a training set, an internal validation set, and two external validation sets. Stone composition was determined by Fourier transform infrared spectroscopy. A total of 1316 radiomic features were extracted from the pre-treatment Computer Tomography images of each patient. Using the least absolute shrinkage and selection operator algorithm, we identified a radiomic signature that achieved favorable discrimination in the training set, which was confirmed in the validation sets. Moreover, we then developed a radiomic model incorporating the radiomic signature, urease-producing bacteria in urine, and urine pH based on multivariate logistic regression analysis. The nomogram showed favorable calibration and discrimination in the training and three validation sets (area under the curve [95% confidence interval], 0.898 [0.840-0.956], 0.832 [0.742-0.923], 0.825 [0.783-0.866], and 0.812 [0.710-0.914], respectively). Decision curve analysis demonstrated the clinical utility of the radiomic model. Thus, our proposed radiomic model can serve as a non-invasive tool to identify urinary infection stones in vivo, which may optimize disease management in urolithiasis and improve patient prognosis.
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http://dx.doi.org/10.1016/j.kint.2021.05.031DOI Listing
June 2021

Long-Term Oncologic Outcomes After Laparoscopic and Robotic Tumor Enucleation for Renal Cell Carcinoma.

Front Oncol 2020 14;10:595457. Epub 2021 Jan 14.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Objectives: Tumor enucleation (TE) optimizes parenchymal preservation with promising short-term oncologic outcomes compared with standard partial nephrectomy (SPN). However, researches/literatures about long-term oncologic outcomes for TE after minimally invasive surgery are scarce. We aim to analyze long-term oncologic outcomes after laparoscopic and robotic tumor enucleation for renal cell carcinoma (RCC).

Patients And Methods: We retrospectively analyzed 146 patients who underwent TE with either laparoscopic or robotic approach for localized RCC in our center. Local recurrence, cancer specific survival (CSS), recurrence free survival (RFS), and overall survival (OS) were the main outcomes. Survival curves were generated using a Kaplan-Meier method. Perioperative outcomes and pathological outcomes were also analyzed.

Results: Overall, 98 male and 48 female patients were eligible for the study. The median tumor size was 3.4 cm with a median R.E.N.A.L. score of seven. Warm ischemia was used in 143 patients with a median ischemia time of 20 min and three patients had zero ischemia. Five patients (3.4%) had major complications (> Clavien IIIa) and only two were related to urinary system. The median global glomerular filtration rate (GFR) preserved after surgery was 93%. Pseudocapsule invasion was reported in 50 tumors (34%) and positive surgical margins were found in 3/146 (2.1%) tumors. At a median follow-up of 66 months, local recurrence happened in two patients (1.4%), and systemic recurrence happened in six patients (4.2%). The 5-year CSS, RFS, OS were 95.7, 89.6, and 91.9%, and the 10-year CSS, RFS, OS were 93.8, 89.6, and 90.0%, respectively.

Conclusion: This study indicates that tumor enucleation with laparoscopic or robotic approach in experienced hands for the treatment of RCC appears oncologically safe with a median follow-up of more than 5 years. Prospective studies with more patients and longer follow-up will be required to further evaluate oncologic safety after TE.
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http://dx.doi.org/10.3389/fonc.2020.595457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841649PMC
January 2021

Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography.

Cell 2020 06 4;181(6):1423-1433.e11. Epub 2020 May 4.

The First People's Hospital of Yunnan Province, Kunmin, China.

Many COVID-19 patients infected by SARS-CoV-2 virus develop pneumonia (called novel coronavirus pneumonia, NCP) and rapidly progress to respiratory failure. However, rapid diagnosis and identification of high-risk patients for early intervention are challenging. Using a large computed tomography (CT) database from 3,777 patients, we developed an AI system that can diagnose NCP and differentiate it from other common pneumonia and normal controls. The AI system can assist radiologists and physicians in performing a quick diagnosis especially when the health system is overloaded. Significantly, our AI system identified important clinical markers that correlated with the NCP lesion properties. Together with the clinical data, our AI system was able to provide accurate clinical prognosis that can aid clinicians to consider appropriate early clinical management and allocate resources appropriately. We have made this AI system available globally to assist the clinicians to combat COVID-19.
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http://dx.doi.org/10.1016/j.cell.2020.04.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196900PMC
June 2020

Association of chromosome 7 aneuploidy measured by fluorescence in situ hybridization assay with muscular invasion in bladder cancer.

Cancer Commun (Lond) 2020 04 12;40(4):167-180. Epub 2020 Apr 12.

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, P. R. China.

Background: The preoperative prediction of muscular invasion status is important for adequately treating bladder cancer (BC) but nevertheless, there are some existing dilemmas in the current preoperative diagnostic accuracy of BC with muscular invasion. Here, we investigated the potential association between the fluorescence in situ hybridization (FISH) assay and muscular invasion among patients with BC. A cytogenetic-clinical nomogram for the individualized preoperative differentiation of muscle-invasive BC (MIBC) from non-muscle-invasive BC (NMIBC) is also proposed.

Methods: All eligible BC patients were preoperatively tested using a FISH assay, which included 4 sites (chromosome-specific centromeric probe [CSP] 3, 7, and 17, and gene locus-specific probe [GLP]-p16 locus). The correlation between the FISH assay and BC muscular invasion was evaluated using the Chi-square tests. In the training set, univariate and multivariate logistic regression analyses were used to develop a cytogenetic-clinical nomogram for preoperative muscular invasion prediction. Then, we assessed the performance of the nomogram in the training set with respect to its discriminatory accuracy and calibration for predicting muscular invasion, and clinical usefulness, which were then validated in the validation set. Moreover, model comparison was set to evaluate the discrimination and clinical usefulness between the nomogram and the individual variables incorporated in the nomogram.

Results: Muscular invasion was more prevalent in BC patients with positive CSP3, CSP7 and CSP17 status (OR [95% CI], 2.724 [1.555 to 4.774], P < 0.001; 3.406 [1.912 to 6.068], P < 0.001 and 2.483 [1.436 to 4.292], P = 0.001, respectively). Radiology-determined tumor size, radiology-determined clinical tumor stage and CSP7 status were identified as independent risk factors of BC muscular invasion by the multivariate regression analysis in the training set. Then, a cytogenetic-clinical nomogram incorporating these three independent risk factors was constructed and was observed to have satisfactory discrimination in the training (AUC 0.784; 95% CI: 0.715 to 0.853) and validation (AUC 0.743; 95% CI: 0.635 to 0.850) set. The decision curve analysis (DCA) indicated the clinical usefulness of our nomogram. In models comparison, using the receiver operator characteristic (ROC) analyses, the nomogram showed higher discriminatory accuracy than any variables incorporated in the nomogram alone and the DCAs also identified the nomogram as possessing the highest net benefits at wide range of threshold probabilities.

Conclusion: CSP7 status was identified as an independent factor for predicting muscular invasion in BC patients and was successfully incorporated in a clinical nomogram combining the results of the FISH assay with clinical risk factors.
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http://dx.doi.org/10.1002/cac2.12017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170658PMC
April 2020

A nomogram for individualized estimation of survival among adult patients with adrenocortical carcinoma after surgery: a retrospective analysis and multicenter validation study.

Cancer Commun (Lond) 2019 11 27;39(1):80. Epub 2019 Nov 27.

Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 510120, Guangdong, P. R. China.

Background: Clinical outcome of adrenocortical carcinoma (ACC) varies because of its heterogeneous nature and reliable prognostic prediction model for adult ACC patients is limited. The objective of this study was to develop and externally validate a nomogram for overall survival (OS) prediction in adult patients with ACC after surgery.

Methods: Based on the data from the Surveillance Epidemiology, and End Results (SEER) database, adults patients diagnosed with ACC between January 1988 and December 2015 were identified and classified into a training set, comprised of 404 patients diagnosed between January 2007 and December 2015, and an internal validation set, comprised of 318 patients diagnosed between January 1988 and December 2006. The endpoint of this study was OS. The nomogram was developed using a multivariate Cox proportional hazards regression algorithm in the training set and its performance was evaluated in terms of its discriminative ability, calibration, and clinical usefulness. The nomogram was then validated using the internal SEER validation, also externally validated using the Cancer Genome Atlas set (TCGA, 82 patients diagnosed between 1998 and 2012) and a Chinese multicenter cohort dataset (82 patients diagnosed between December 2002 and May 2018), respectively.

Results: Age at diagnosis, T stage, N stage, and M stage were identified as independent predictors for OS. A nomogram incorporating these four predictors was constructed using the training set and demonstrated good calibration and discrimination (C-index 95% confidence interval [CI], 0.715 [0.679-0.751]), which was validated in the internal validation set (C-index [95% CI], 0.672 [0.637-0.707]), the TCGA set (C-index [95% CI], 0.810 [0.732-0.888]) and the Chinese multicenter set (C-index [95% CI], 0.726 [0.633-0.819]), respectively. Encouragingly, the nomogram was able to successfully distinguished patients with a high-risk of mortality in all enrolled patients and in the subgroup analyses. Decision curve analysis indicated that the nomogram was clinically useful and applicable.

Conclusions: The study presents a nomogram that incorporates clinicopathological predictors, which can accurately predict the OS of adult ACC patients after surgery. This model and the corresponding risk classification system have the potential to guide therapy decisions after surgery.
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http://dx.doi.org/10.1186/s40880-019-0426-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882048PMC
November 2019

Development of a noninvasive tool to preoperatively evaluate the muscular invasiveness of bladder cancer using a radiomics approach.

Cancer 2019 12 30;125(24):4388-4398. Epub 2019 Aug 30.

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Background: Bladder cancer (BCa) can be divided into muscle-invasive BCa (MIBC) and non-muscle-invasive BCa (NMIBC). Whether the tumor infiltrates the detrusor muscle is a critical determinant of disease management in patients with BCa. However, the current preoperative diagnostic accuracy of muscular invasiveness is less than satisfactory. The authors report a radiomic-clinical nomogram for the individualized preoperative differentiation of MIBC from NMIBC.

Methods: In total, 2602 radiomics features were extracted from whole bladder tumors and the basal part of the lesions on T2-weighted magnetic resonance imaging. Then, a radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm in the training set (n = 130). Furthermore, a radiomic-clinical nomogram was developed incorporating the radiomics signature and selected clinical predictors based on a multivariable logistic regression analysis. The performance of the nomogram (discrimination, calibration, and clinical usefulness) was assessed and validated in an independent validation set (n = 69).

Results: The radiomics signature, consisting of 23 selected features, showed good discrimination in the training and validation sets (area under the curve [AUC], 0.913 and 0.874, respectively). Incorporating the radiomics signature and magnetic resonance imaging-determined tumor size, the radiomic-clinical nomogram showed favorable calibration and discrimination in the training set with an AUC of 0.922, which was confirmed in the validation set (AUC, 0.876). Decision curve analysis and net reclassification improvement and integrated discrimination improvement indices (net reclassification improvement, 0.338, integrated discrimination improvement, 0.385) demonstrated the clinical usefulness of the nomogram.

Conclusions: The proposed noninvasive radiomic-clinical nomogram can increase the accuracy of preoperatively discriminating MIBC from NMIBC, which may aid in clinical decision making and improve patient prognosis.
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http://dx.doi.org/10.1002/cncr.32490DOI Listing
December 2019

Development and Validation of an MRI-Based Radiomics Signature for the Preoperative Prediction of Lymph Node Metastasis in Bladder Cancer.

EBioMedicine 2018 Aug 2;34:76-84. Epub 2018 Aug 2.

Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, PR China; State Key Laboratory of Oncology in South China, PR China. Electronic address:

Background: Preoperative lymph node (LN) status is important for the treatment of bladder cancer (BCa). However, a proportion of patients are at high risk for inaccurate clinical nodal staging by current methods. Here, we report an accurate magnetic resonance imaging (MRI)-based radiomics signature for the individual preoperative prediction of LN metastasis in BCa.

Methods: In total, 103 eligible BCa patients were divided into a training set (n = 69) and a validation set (n = 34). And 718 radiomics features were extracted from the cancerous volumes of interest (VOIs) on T2-weighted MRI images. A radiomics signature was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm in the training set, whose performance was assessed and then validated in the validation set. Stratified analyses were also performed. Based on the multivariable logistic regression analysis, a radiomics nomogram was developed incorporating the radiomics signature and selected clinical predictors. Discrimination, calibration and clinical usefulness of the nomogram were assessed.

Findings: Consisting of 9 selected features, the radiomics signature showed a favorable discriminatory ability in the training set with an AUC of 0.9005, which was confirmed in the validation set with an AUC of 0.8447. Encouragingly, the radiomics signature also showed good discrimination in the MRI-reported LN negative (cN0) subgroup (AUC, 0.8406). The nomogram, consisting of the radiomics signature and the MRI-reported LN status, showed good calibration and discrimination in the training and validation sets (AUC, 0.9118 and 0.8902, respectively). The decision curve analysis indicated that the nomogram was clinically useful.

Interpretation: The MRI-based radiomics nomogram has the potential to be used as a non-invasive tool for individualized preoperative prediction of LN metastasis in BCa. External validation is further required prior to clinical implementation.
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http://dx.doi.org/10.1016/j.ebiom.2018.07.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116473PMC
August 2018

Computed tomography and magnetic resonance imaging evaluation of pelvic lymph node metastasis in bladder cancer.

Chin J Cancer 2018 01 26;37(1). Epub 2018 Jan 26.

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong, P. R. China.

Background: Accurate evaluation of lymph node metastasis in bladder cancer (BCa) is important for disease staging, treatment selection, and prognosis prediction. In this study, we aimed to evaluate the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) for metastatic lymph nodes in BCa and establish criteria of imaging diagnosis.

Methods: We retrospectively assessed the imaging characteristics of 191 BCa patients who underwent radical cystectomy. The data regarding size, shape, density, and diffusion of the lymph nodes on CT and/or MRI were obtained and analyzed using Kruskal-Wallis test and χ test. The optimal cutoff value for the size of metastatic node was determined using the receiver operating characteristic (ROC) curve analysis.

Results: A total of 184 out of 3317 resected lymph nodes were diagnosed as metastatic lymph nodes. Among 82 imaging-detectable lymph nodes, 51 were confirmed to be positive for metastasis. The detection rate of metastatic nodes increased along with more advanced tumor stage (P < 0.001). Once the ratio of short- to long-axis diameter ≤ 0.4 or fatty hilum was observed in lymph nodes on imaging, it indicated non-metastases. Besides, lymph nodes with spiculate or obscure margin or necrosis indicated metastases. Furthermore, the short diameter of 6.8 mm was the optimal threshold to diagnose metastatic lymph node, with the area under ROC curve of 0.815.

Conclusions: The probability of metastatic nodes significantly increased with more advanced T stages. Once lymph nodes are detected on imaging, the characteristic signs should be paid attention to. The short diameter > 6.8 mm may indicate metastatic lymph nodes in BCa.
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http://dx.doi.org/10.1186/s40880-018-0269-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785867PMC
January 2018

A Radiomics Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Bladder Cancer.

Clin Cancer Res 2017 Nov 5;23(22):6904-6911. Epub 2017 Sep 5.

Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.

To develop and validate a radiomics nomogram for the preoperative prediction of lymph node (LN) metastasis in bladder cancer. A total of 118 eligible bladder cancer patients were divided into a training set ( = 80) and a validation set ( = 38). Radiomics features were extracted from arterial-phase CT images of each patient. A radiomics signature was then constructed with the least absolute shrinkage and selection operator algorithm in the training set. Combined with independent risk factors, a radiomics nomogram was built with a multivariate logistic regression model. Nomogram performance was assessed in the training set and validated in the validation set. Finally, decision curve analysis was performed with the combined training and validation set to estimate the clinical usefulness of the nomogram. The radiomics signature, consisting of nine LN status-related features, achieved favorable prediction efficacy. The radiomics nomogram, which incorporated the radiomics signature and CT-reported LN status, also showed good calibration and discrimination in the training set [AUC, 0.9262; 95% confidence interval (CI), 0.8657-0.9868] and the validation set (AUC, 0.8986; 95% CI, 0.7613-0.9901). The decision curve indicated the clinical usefulness of our nomogram. Encouragingly, the nomogram also showed favorable discriminatory ability in the CT-reported LN-negative (cN0) subgroup (AUC, 0.8810; 95% CI, 0.8021-0.9598). The presented radiomics nomogram, a noninvasive preoperative prediction tool that incorporates the radiomics signature and CT-reported LN status, shows favorable predictive accuracy for LN metastasis in patients with bladder cancer. Multicenter validation is needed to acquire high-level evidence for its clinical application. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-1510DOI Listing
November 2017

The Effect of Prophylactic Lamivudine plus Adefovir Therapy Compared with Lamivudine Alone in Preventing Hepatitis B Reactivation in Lymphoma Patients with High Baseline HBV DNA during Chemotherapy.

PLoS One 2016 6;11(10):e0164210. Epub 2016 Oct 6.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.

Prophylactic antiviral therapy is essential for lymphoma patients with high baseline HBV DNA who undergo cytotoxic chemotherapy. However, there are limited data on the optimal options. The present study was designed to compare the efficacy of prophylactic lamivudine (LAM) with lamivudine plus adefovir dipivoxil (LAM+ADV) in preventing hepatitis B virus (HBV) reactivation in lymphoma with, pre-chemotherapy HBV DNA load ≥2000 IU/ml. We retrospectively analyzed the medical records of 86 lymphoma patients with baseline HBV DNA load ≥2000 IU/ml during chemotherapy and received LAM or LAM+ADV as prophylaxis between January 1, 2008 and November 30, 2014 at Sun Yat-sen University Cancer Center, China. Sixty-five patients received LAM and 21 received LAM+ADV. The rate was significantly lower in the LAM+ADV group compared with the LAM group for HBV reactivation (23.8% vs 55.4%; p = 0.012), while no difference was observed between the two groups in patients for HBV-related hepatitis (21.3% vs 33.3%; p   =  0.349), and chemotherapy disruption (10.9% vs 19.0%; p = 0.337). In a multivariate analysis of factors associated with HBV reactivation in these patients, LAM+ADV treatment and HBeAg negative were the independent protective factors. Therefore, LAM+ADV should be considered for antiviral prophylaxis in lymphoma patients with pre-chemotherapy HBV DNA load ≥2000 IU/ml. Further study is warranted to confirm these findings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164210PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053414PMC
June 2017

High CD204+ tumor-infiltrating macrophage density predicts a poor prognosis in patients with urothelial cell carcinoma of the bladder.

Oncotarget 2015 Aug;6(24):20204-14

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, PR China.

Macrophages (Mφs) are a major cell type that can infiltrate solid tumors and exhibit distinct phenotypes in different tumor microenvironments. This study attempted to investigate the prognostic values of various tumor-infiltrating Mφ phenotypes in patients with urothelial cell carcinoma of the bladder (UCB), with a focus on Mφ tissue microlocalization. Mφs were assessed by immunohistochemistry in tissues from 302 UCB patients using CD68 as a pan-Mφ marker, and CD204 and CD169 as robust pro- and anti-tumoral Mφ phenotype markers, respectively. Our data showed that these Mφ phenotypes were predominately distributed in stromal (ST) rather than in intratumoral (INT) regions (all P < 0.0001). Surprisingly, CD204 and CD169 can be co-expressed by the same CD68+ Mφs. Kaplan-Meier analysis revealed that all INT- and ST-infiltrating CD204+ or CD169+ Mφ densities were inversely associated with overall survival (all P < 0.01). By multivariate analysis, ST-infiltrating CD204+ Mφ density emerged as an independent prognostic factor for overall survival (HR, 1.981; P = 0.022). Moreover, the density of ST-infiltrating CD204+ Mφs was positively associated with the tumor size (P = 0.001), tumor stage (P < 0.0001), nodal metastasis (P < 0.0001), and histological grade (P < 0.0001). Our findings suggest that CD204+ Mφs might play detrimental protumoral roles and represent the predominant Mφ phenotype in human bladder cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652998PMC
http://dx.doi.org/10.18632/oncotarget.3887DOI Listing
August 2015

PBRM1 suppresses bladder cancer by cyclin B1 induced cell cycle arrest.

Oncotarget 2015 Jun;6(18):16366-78

Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.

Growing evidence indicates that dys-regulation of PBRM1 contributes to tumorigenesis. However, little is known about the biological function of PBRM1 in the development or progression of bladder cancer. In this study, we aimed to elucidate the pathophysiological role of PBRM1 in bladder cancer. We assessed the expression of PBRM1 in 64 bladder cancer tissue samples with matching normal tissues. We explored the biological functions of PBRM1 both in vitro and in vivo. Mutational status of PBRM1 was analyzed. Effect of PBRM1 on cell cycle was evaluated. qRT-PCR and Western blot were carried out to evaluate the expression of cyclins affected by PBRM1. Our results showed that PBRM1 expression was significantly reduced in bladder cancer cells and tissues compared to their normal counterparts. The reduced expression of PBRM1 was associated with advanced tumor stage, low differentiation grade and worse patient outcome. Further functional analysis demonstrated that PBRM1 suppressed bladder cancer cell proliferation, migration, colony formation in vitro and tumorigenicity in vivo. Genetic alteration analysis showed no amino-acid sequence altering mutations. We found that PBRM1 could block the G2/M transition by repressing cyclin B1. Our data indicated that PBRM1 functions as a tumor suppressor in bladder cancer by repressing cyclin B1 expression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599275PMC
http://dx.doi.org/10.18632/oncotarget.3879DOI Listing
June 2015

Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells.

Biochem Biophys Res Commun 2015 May 17;460(2):380-5. Epub 2015 Mar 17.

Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People's Republic of China. Electronic address:

Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients.
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http://dx.doi.org/10.1016/j.bbrc.2015.03.042DOI Listing
May 2015

CD103+ Tumor Infiltrating Lymphocytes Predict a Favorable Prognosis in Urothelial Cell Carcinoma of the Bladder.

J Urol 2015 Aug 6;194(2):556-62. Epub 2015 Mar 6.

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China. Electronic address:

Purpose: CD8(+) TILs at different tumor sites have diverse clinical attributes, which might result from distinct tumor microenvironments that promote differentiation into distinct subsets. However, only a few markers have been identified that can define CD8(+) T-cell subsets. CD103 is a marker of tissue resident memory CD8(+) T cells. In this retrospective study we investigated the cellular source and clinical significance of CD103 expression in urothelial cell carcinoma of bladder tissues in situ.

Materials And Methods: Immunohistochemistry and immunofluorescence were used to identify the cellular source of CD103 in bladder urothelial cell carcinoma tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall and recurrence-free survival in 302 patients with bladder urothelial cell carcinoma.

Results: CD8(+) T cells but not natural killer cells accounted for most CD103 expressing cells in bladder urothelial cell carcinoma tissues. Notably CD103(+) cells were predominantly located in intratumor regions rather than in associated stroma (p < 0.0001). The density of intratumor CD103(+) TILs was inversely associated with tumor size (p < 0.0001) and could represent a favorable prognostic predictor of overall and recurrence-free survival (p = 0.002 and 0.011, respectively). Moreover, intratumor CD103(+) TILs were positively associated with the expression of cognate ligand E-cadherin in intratumor regions of bladder urothelial cell carcinoma tissues (p = 0.008).

Conclusions: Our findings suggest that CD8(+) T cells might have a significant role in tumor immunity by expressing CD103 in intratumor regions of bladder urothelial cell carcinoma tissues. Intratumor CD103(+) TILs could potentially serve as a prognostic marker in patients with bladder urothelial cell carcinoma.
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http://dx.doi.org/10.1016/j.juro.2015.02.2941DOI Listing
August 2015
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