5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer.

BACKGROUND: Depicting the heterogeneity and functional characteristics of the tumor microenvironment (TME) is necessary to achieve precision medicine for bladder cancer (BLCA). Although classical molecular subtypes effectively reflect TME heterogeneity and characteristics, their clinical application is limited by several issues. METHODS: In this study, we integrated the Xiangya cohort and multiple external BLCA cohorts to develop a novel 5-methylcytosine (5mC) regulator-mediated molecular subtype system and a corresponding quantitative indicator, the 5mC score. Unsupervised clustering was performed to identify novel 5mC regulator-mediated molecular subtypes. The principal component analysis was applied to calculate the 5mC score. Then, we correlated the 5mC clusters (5mC score) with classical molecular subtypes, immunophenotypes, clinical outcomes, and therapeutic opportunities in BLCA. Finally, we performed pancancer analyses on the 5mC score. RESULTS: Two 5mC clusters, including 5mC cluster 1 and cluster 2, were identified. These novel 5mC clusters (5mC score) could accurately predict classical molecular subtypes, immunophenotypes, prognosis, and therapeutic opportunities of BLCA. 5mC cluster 1 (high 5mC score) indicated a luminal subtype and noninflamed phenotype, characterized by lower anticancer immunity but better prognosis. Moreover, 5mC cluster 1 (high 5mC score) predicted low sensitivity to cancer immunotherapy, neoadjuvant chemotherapy, and radiotherapy, but high sensitivity to antiangiogenic therapy and targeted therapies, such as blocking the ß-catenin, FGFR3, and PPAR-γ pathways. CONCLUSIONS: The novel 5mC regulator-based subtype system reflects many aspects of BLCA biology and provides new insights into precision medicine in BLCA. Furthermore, the 5mC score may be a generalizable predictor of immunotherapy response and prognosis in pancancers.

Prognostic factors in patients with penile cancer after surgical management.

PURPOSE: To examine the possible prognostic factors in patients with penile cancer after surgical management and to identify the independent predictive factors of the prognosis. MATERIALS AND METHODS: Clinical data of 135 patients with penile cancer who underwent surgical management in two medical centers were collected. Follow-up data were available for 103 patients. Possible prognostic factors including patient's age; smoking or not; course of disease; phimosis or not; type of surgery; tumor stage; nodal stage; tumor grade and pathological lymph nodes metastasis were retrospectively analyzed by univariate and multivariate analyses with Cox regression. RESULTS: Five-year cancer-specific survival (CSS) and 1-year CSS were 88.5 and 98.1%, respectively. Univariate Cox analysis revealed that nodal stage and pathological lymph nodes metastasis were significant prognostic factors. Multivariate Cox analysis revealed pathological lymph nodes metastasis was the independent predictive factor of the prognosis. CONCLUSION: Pathological lymph nodes metastasis is the independent predictive factor worsening the prognosis in patients with penile cancer.

Localized chromophobe renal cell carcinoma: preoperative imaging judgment and laparoscopic simple enucleation for treatment.

OBJECTIVE: To evaluate the preoperative imaging manifestation and therapeutic effect of laparoscopic simple enucleation (SE) for localized chromophobe renal cell carcinoma (chRCC). MATERIALS AND METHODS: Clinical data of 36 patients who underwent laparoscopic SE of localized chRCC at our institute were retrospectively analyzed. All patients underwent preoperative renal protocol CT (unenhanced, arterial, venous, and delayed images). CT scan characteristics were evaluated. After intraoperative occlusion of the renal artery, the tumor was free bluntly along the pseudocapsule and enucleated totally. The patients were followed up regularly after the operation. RESULTS: Mean tumor diameter was 3.9±1.0 cm, 80% of tumors were homogeneous and all the tumors had complete pseudocapsule. The attenuation values were slightly lower than normal renal cortex and degree of enhancement of the tumors were significantly lower than normal renal cortex. Mean operation time was 104.3±18.2 min. Mean warm ischemia time (WIT) was 21.3±3.5 min. Mean blood loss was 78.6±25.4 mL. No positive surgical margin was identified. Mean postoperative hospital stay was 5.3±1.5 d. Hematuria occurred in 3 patients and all disappeared within 3 days. After a mean follow-up of 32.1±20.6 months, no patient had local recurrence or metastatic progression. CONCLUSION: Localized chRCCs have a great propensity for homogeneity and complete pseudocapsule. The attenuation values were slightly lower than normal renal cortex and small degree of enhancement. Laparoscopic SE is a safe and effective treatment for localized chRCC. The oncological results were satisfactory.

miR-616-5p Promotes Invasion and Migration of Bladder Cancer via Downregulating NR2C2 Expression.

BACKGROUND: MicroRNAs, small non-coding RNA molecules with about 22 nucleotides in length, play a significant role in the development of bladder cancer. Previous studies found that miR-616-5p could promote the progress of cancers. However, its role in bladder cancer remains unclear. In the study, we aimed to demonstrate how miR-616-5p impacts the invasion and migration of bladder cancer and its potential downstream targets. METHODS: Firstly, qRT-PCR was used to detect the expression of miR-616-5p in normal bladder uroepithelial cell lines and bladder cancer cell lines. Then, chamber-transwell invasion and wound healing migration assays were used to detect the roles of miR-616-5p and NR2C2 in invasion and migration. Subsequently, Western blot was used to evaluate the regulation effects of miR-616-5p and NR2C2. Finally, luciferase assays were performed to manifest the mechanism of miR-616-5p and NR2C2 regulation. RESULTS: We found that miR-616-5p was upregulated in bladder cancer, and it could promote the invasion and migration of bladder cancer in vitro. Moreover, we demonstrated that NR2C2 was a downstream target of miR-616-5p. miR-616-5p could inhibit the expression of NR2C2 by binding to the 3'UTR of NR2C2 mRNA. Importantly, patients with a high expression of NR2C2 showed better prognoses in bladder cancer. CONCLUSIONS: This study identifies that miR-616-5p can promote bladder cancer progression via altering the expression of NR2C2. Therefore, identifying miR-616-5p expression levels might be a useful strategy for developing potential therapeutic targets in bladder cancer.

Emerging Biomarkers for Predicting Bladder Cancer Lymph Node Metastasis.

Bladder cancer is one of the leading causes of cancer deaths worldwide. Early detection of lymph node metastasis of bladder cancer is essential to improve patients' prognosis and overall survival. Current diagnostic methods are limited, so there is an urgent need for new specific biomarkers. Non-coding RNA and m6A have recently been reported to be abnormally expressed in bladder cancer related to lymph node metastasis. In this review, we tried to summarize the latest knowledge about biomarkers, which predict lymph node metastasis in bladder cancer and their mechanisms. In particular, we paid attention to the impact of non-coding RNA on lymphatic metastasis of bladder cancer and its specific molecular mechanisms, as well as some prediction models based on imaging, pathology, and biomolecules, in an effort to find more accurate diagnostic methods for future clinical application.

Recurrence factors in patients with Keratinizing squamous metaplasia of the bladder after surgical management: a single-center retrospective study.

BACKGROUND: Keratinizing squamous metaplasia (KSM) is a clinically heterogeneous disease that lacks research that provide definitive recurrent risk factors. Therefore, we identified the recurrence factors in patients with KSM of the bladder after transurethral resection (TUR). We also attempted to investigate the association between KSM and bladder cancer. METHODS: Clinical information of 257 patients diagnosed with KSM who underwent TUR in Xiangya Hospital from January 2010 to November 2018 were retrospectively collected. Clinical information was available for follow-up of 223 patients. To determine the risk factors for recurrence, we conducted univariate and multivariate cox regression analysis respectively. To explore the association between KSM and bladder cancer, we used clinical follow-up data. RESULTS: The median follow-up time is 49 (IQR, 12-121) months. Five-year recurrence-free rate (RFR) and 1-year RFR were 86.1% and 91.9%, respectively. Thirty-one patients (13.9%) relapsed of KSM after a median follow-up of 49 months (range, 12-121 months), and none of them developed subsequent bladder cancer. Univariate Cox analysis indicated that urinary tract infection [hazard ratio (HR) =2.111; 95% confidence interval (CI): 1.043-4.271; P=0.038], and atypical urothelial hyperplasia of the bladder (HR =4.191; 95% CI: 2.006-8.756; P<0.001) were significant recurrence factors. Multivariate Cox analysis suggested that atypical urothelial hyperplasia of the bladder (HR =3.506; 95% CI: 1.663-7.392; P=0.001) was the independent risk factor for postoperative recurrence of KSM. CONCLUSIONS: The recurrence rate in patients with KSM was about 13.9%, and atypical urothelial hyperplasia of the bladder was the independent risk factor in patients with KSM recurrence. In cases with bladder atypical urothelial hyperplasia, close follow-ups are necessary. Also, we demonstrated that KSM did not increase the subsequent risk of bladder cancer.

PMEPA1 Is a Prognostic Biomarker That Correlates With Cell Malignancy and the Tumor Microenvironment in Bladder Cancer.

Prostate transmembrane protein androgen induced 1 (PMEPA1) has been reported to promote cancer progression, but the potential role of PMEPA1 in bladder cancer (BLCA) remains elusive. We assess the role of PMEPA1 in BLCA, via a publicly available database and in vitro study. PMEPA1 was identified from 107 differentially expressed genes (DEGs) to have prognostic value. GO, KEGG, and GSEA analysis indicated that PMEPA1 was involved in cancer progression and the tumor microenvironment (TME). Then bioinformatical analysis in TCGA, GEO, TIMER, and TISIDB show a positive correlation with the inflammation and infiltration levels of three tumor-infiltrating immune cells (TAMs, CAFs, and MDSCs) and immune/stromal scores in TME. Moreover, in vitro study revealed that PMEPA1 promotes bladder cancer cell malignancy. Immunohistochemistry and survival analysis shed light on PMEPA1 potential to be a novel biomarker in predicting tumor progression and prognosis. At last, we also analyzed the role of PMEPA1 in predicting the molecular subtype and the response to several treatment options in BLCA. We found that PMEPA1 may be a novel potential biomarker to predict the progression, prognosis, and molecular subtype of BLCA.

N6-Methyladenosine in Cancer Immunotherapy: An Undervalued Therapeutic Target.

N6-methylation of adenosine (m6A), a post-transcriptional regulatory mechanism, is the most abundant nucleotide modification in almost all types of RNAs. The biological function of m6A in regulating the expression of oncogenes or tumor suppressor genes has been widely investigated in various cancers. However, recent studies have addressed a new role of m6A modification in the anti-tumor immune response. By modulating the fate of targeted RNA, m6A affects tumor-associated immune cell activation and infiltration in the tumor microenvironment (TME). In addition, m6A-targeting is found to affect the efficacy of classical immunotherapy, which makes m6A a potential target for immunotherapy. Although m6A modification together with its regulators may play the exact opposite role in different tumor types, targeting m6A regulators has been shown to have wide implications in several cancers. In this review, we discussed the link between m6A modification and tumor with an emphasis on the importance of m6A in anti-tumor immune response and immunotherapy.

Siglec15 shapes a non-inflamed tumor microenvironment and predicts the molecular subtype in bladder cancer.

Rationale: Siglec15 is an emerging target for normalization cancer immunotherapy. However, pan-cancer anti-Siglec15 treatment is not yet validated and the potential role of Siglec15 in bladder cancer (BLCA) remains elusive. Methods: We comprehensively evaluated the expression pattern and immunological role of Siglec15 using pan-cancer analysis based on RNA sequencing data obtained from The Cancer Genome Atlas. We then systematically correlated Siglec15 with immunological characteristics in the BLCA tumor microenvironment (TME), including immunomodulators, cancer immunity cycles, tumor-infiltrating immune cells (TIICs), immune checkpoints, and T cell inflamed score. We also analyzed the role of Siglec15 in predicting the molecular subtype and the response to several treatment options in BLCA. Our results were validated in several public cohorts as well as our BLCA tumor microarray cohort, the Xiangya cohort. We developed an immune risk score (IRS), validated it, and tested its ability to predict the prognosis and response to cancer immunotherapy. Results: We found that Siglec15 was specifically overexpressed in the TME of various cancers. We hypothesize that Siglec15 designs a non-inflamed TME in BLCA based on the evidence that Siglec15 negatively correlated with immunomodulators, TIICs, cancer immunity cycles, immune checkpoints, and T cell inflamed score. Bladder cancer with high Siglec15 expression was not sensitive to cancer immunotherapy, but exhibited a higher incidence of hyperprogression. High Siglec15 levels indicated a luminal subtype of BLCA characterized by lower immune infiltration, lower response to cancer immunotherapy and neoadjuvant chemotherapy, but higher response to anti-angiogenic therapy and targeted therapies such as blocking Siglec15, ß-catenin, PPAR-γ, and FGFR3 pathways. Notably, a combination of anti-Siglec15 and cancer immunotherapy may be a more effective strategy than monotherapy. IRS can accurately predict the prognosis and response to cancer immunotherapy. Conclusions: Anti-Siglec15 immunotherapy might be suitable for BLCA treatment as Siglec15 correlates with a non-inflamed TME in BLCA. Siglec15 could also predict the molecular subtype and the response to several treatment options.

Infertility duration and pre-operative sperm progressive motility are significant factors of spontaneous pregnancy after varicocele repair.

PROBLEM: Varicocele may lead to testicular dysfunction and male infertility. Varicocelectomy can improve both semen quality and post-operative spontaneous pregnancy. However, different patients benefit distinctly from the surgery. Therefore, the study aims at examining the possible factors of spontaneous pregnancy after laparoscopic varicocelectomy in infertile men. METHOD OF STUDY: Clinical data of 196 infertile men who underwent laparoscopic varicocelectomy at our institute were collected from December 2013 to February 2019. Follow-up data were available for 148 patients. All the patients were treated with laparoscopic varicocelectomy performed by experienced urological doctors. Possible pre-operative factors of spontaneous pregnancy after laparoscopic varicocelectomy were retrospectively analyzed. RESULTS: After a mean follow-up of 29.1 ± 12.6 months (range 12-74 months), 74 (50%) of couples achieved spontaneous pregnancy. Univariate analysis revealed that short infertility duration, secondary infertility, and high sperm progressive motility were significant predictors of spontaneous pregnancy after laparoscopic varicocelectomy. Multivariate analysis revealed that short infertility duration (≤2 years) and high sperm progressive motility (>30%) were independent predictors. CONCLUSION: Both infertility duration and pre-operative sperm progressive motility could serve as independent factors of spontaneous pregnancy after laparoscopic varicocelectomy.

A nomogram incorporating PD-L1, NLR, and clinicopathologic features to predict inguinal lymph node metastasis in penile squamous cell carcinoma.

BACKGROUND: Accurate preoperative prediction of inguinal lymph node metastasis (LNM) aids in clinical decision making, especially for patients with penile cancer with clinically negative lymph nodes. We aim to develop a nomogram to predict the preoperative risk of LNM by incorporating clinicopathologic features and tumor biomarkers. METHODS: Eighty-four patients with penile cancer with clinically negative lymph nodes were enrolled. The programmed death ligand 1 (PD-L1) expression profile was detected by immunohistochemistry. The neutrophil-to-lymphocyte ratio (NLR) was calculated based on parameters of a routine blood examination. Multivariate logistic regression analysis was utilized to construct predictive nomograms for LNM based on data of 64 patients. The nomogram performance was assessed for calibration, discrimination, and clinical use. RESULTS: Tumor grade, lymphovascular invasion, PD-L1, and NLR were independent predictors of LNM. Then, 4 prediction models were constructed. Clinical model included tumor grade and lymphovascular invasion. NLR model was built by adding the NLR to clinical model. PD-L1 model was built by adding the PD-L1 to clinical model. Finally, a combined model was built by adding both PD-L1 and NLR to clinical model. Combined model showed the best performance compared with other models. It showed good discrimination with a C-index of 0.89, and good calibration. In addition, decision curve analysis suggested that model 4 was clinically useful. CONCLUSIONS: We developed a nomogram that incorporated tumor grade, lymphovascular invasion, PD-L1, and NLR that could be conveniently used to predict the preoperative individualized risk of inguinal LNM in patients with penile cancer.

Development and validation of a predictive nomogram for the risk of recurrence in patients with cystitis glandularis.

BACKGROUND: Most patients with cystitis glandularis (CG) suffer from recurrence after primary treatment. Therefore, we performed this multicenter study to clarify the recurrent risk factors and constructed a predictive nomogram for the risk of recurrence. Also, we try to investigate the correlation between CG and bladder cancer. METHODS: Consecutive patients with pathologically confirmed CG were divided into training and validation sets. Clinicopathological characters were collected from electronic medical records. Uni- and multivariate logistic regression analyses were used to identify independent risk factors of CG recurrence in the training set. The predictive nomogram was developed by incorporating these independent factors and histological subtype. The performance of the nomogram was assessed and validated with respects to its calibration, discrimination, and clinical usefulness. The risk of developing subsequent bladder cancer was analyzed from the follow-up data. RESULTS: Ultimately, 278 eligible patients were included and were allocated to a training set (n=190) and a validation set (n=88). Of them, 165 (59.35%) patients experienced CG recurrence, and none showed evidence of subsequent bladder carcinoma during a median (IQR) follow-up time of 27 months (14-57 months). Results of multivariate analysis showed that urinary infections, long-term indwelling catheter usage, urinary calculus, squamous metaplasia, and atypical hyperplasia were independent risk factors of CG recurrence. The C-index (95% CI) of the nomogram was 0.76 (0.69-0.83) in the training set and 0.72 (0.61-0.83) in the validation set. A decision curve analysis (DCA) demonstrated that this predictive nomogram was clinically useful. CONCLUSIONS: We developed and validated a nomogram to predict the individualized risk of CG recurrence. Also, we demonstrated that neither intestinal nor typical CG increased the consequent risk of bladder cancer during the follow-up period.

A preoperative nomogram predicting the pseudocapsule status in localized renal cell carcinoma.

BACKGROUND: Tumor enucleation (TE) surgery for localized renal cell carcinoma (RCC) relies on a complete peritumoral pseudocapsule (PC). Study objective was to develop a preoperative model to predict PC status. METHODS: The prediction model was developed in a cohort that consisted of 170 patients with localized RCC, and data was gathered from 2010 to 2015. Multivariable logistic regression analysis and R were used to generate this prediction model. The statistical performance was assessed with respect to the calibration, discrimination, and clinical usefulness. RESULTS: The prediction model incorporated the systemic inflammatory markers [neutrophil-lymphocyte ratio (NLR); albumin-globulin ratio (AGR)], CT imaging features (tumor size and necrosis), and clinical risk factors (BMI). The model showed good discrimination, with a C-index of 0.85 (0.78-0.91), and good calibration (P=0.60). The sensitivity and specificity were 62% and 94% respectively. Decision curves and clinical impact curve demonstrated that the current model was clinically useful. CONCLUSIONS: We constructed a model that incorporated both the systematic inflammatory markers and clinical risk factors. It can be conveniently used to preoperatively predict the individualized risk of PC invasion and identify the best candidates to receive TE surgery.

Low Expression of ATM Indicates a Poor Prognosis in Clear Cell Renal Cell Carcinoma.

INTRODUCTION: The study was carried out to examine the expression of ataxia telangiectasia mutant (ATM) of clear cell renal cell carcinoma (ccRCC), and to explore the relationship between the expression of ATM and the clinicopathologic parameters and prognosis of ccRCC. MATERIALS AND METHODS: Clinicopathologic data of the patients with ccRCC were collected from January 2011 to August 2015 in Xiangya Hospital, Central South University. The immunohistochemical method was used to detect the expression of ATM in ccRCC and adjacent tissues. The Kaplan-Meier survival method and log-rank test were used to analyze the relationship between ATM expression and the survival time of the patients with ccRCC. Univariate and multivariate Cox regression analysis was used to evaluate the risk factors for the prognosis of ccRCC. RESULTS: A total of 110 patients were selected in this study, including 73 men and 37 women. The expression of ATM in ccRCC is significantly lower than that in adjacent tissues. Further analysis found that the expression of ATM in the ccRCC tissues above grade II was lower than that of grade II or below. Kaplan-Meier survival analysis showed that the total survival time of the ATM low expression group was significantly shorter than that of the ATM high expression group. The multivariate Cox regression analysis showed that expression of ATM and clinical stage were independent factors affecting the prognosis of ccRCC. CONCLUSION: ATM expression level could serve as an independent risk factor for the prognosis of ccRCC and could be considered as a potential therapeutic target of ccRCC.

Predictors of inguinal lymph node metastasis in penile cancer patients: a meta-analysis of retrospective studies.

PURPOSE: Inguinal lymph node metastasis (LNM) is one of the most significant prognostic factors for patients with penile cancer. This study aimed to identify potential predictors of inguinal LNM. PATIENTS AND METHODS: A comprehensive search of the PubMed, Embase, and Cochrane Library databases for studies that reported predictors of inguinal LNM in penile cancer was performed. Finally, we selected 42 eligible studies with 4,802 patients. Accumulative analyses of odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were performed. All analyses were performed by using Review Manager software version 5.3. RESULTS: Among the 4,802 patients, 1,706 (36%) were diagnosed with inguinal LNM. Predictors of LNM included two categories: tumor-associated biomarkers and invasive clinicopathologic characteristics. Biomarker-specific predictors: the program death ligand 1 (PD-L1) overexpression (OR=2.55, p=0.002), higher neutrophil-to-lymphocyte ratio (NLR) (OR=4.22, p=0.010), higher C-reactive protein (CRP) (OR=4.78, p<0.001), squamous cell carcinoma antigen (SCC-Ag) overexpression (OR=8.52, p<0.001), P53 protein overexpression (OR=3.57, p<0.001). Clinicopathological predictors: positive clinical lymph node (cN+) (OR=5.86, p<0.001), high-risk histopathological subtype (OR=14.63, p<0.001) and intermediate-risk subtype (OR=3.37, p<0.001), vertical growth pattern (OR=1.97, p=0.020), higher stage (AJCC: OR=3.66, p<0.001; UICC: OR=2.43, p<0.001), higher tumor grade (OR=3.37, p<0.001), tumor size (>3 cm) (OR=2.00, p=0.002), LVI (OR=3.37, p<0.001), invasion depth (>5 mm) (OR=2.58, p=0.002), nerve invasion (OR=2.84, p<0.001), corpora cavernosum invasion (OR=2.22, p<0.001), corpus spongiosum invasion (OR=1.73, p=0.002) and urethra invasion (OR=1.81, p=0.030). CONCLUSION: Current meta-analysis conclusively identified valuable predictors of inguinal LNM for patients with penile cancer. However, high-quality studies are warranted to further validate our conclusions. The intrinsic link between these predictors needs to be further investigated to create an accurate mathematical prediction model for LNM.

UCA1 promotes cell viability, proliferation and migration potential through UCA1/miR-204/CCND2 pathway in primary cystitis glandularis cells.

Cystitis glandularis (CG) is an unusual proliferative disorder of the urinary bladder. Increasing evidences demonstrated that long non-coding RNAs (lncRNAs) play important roles in a variety of cellular progresses. However, there are rarely reports about the role and underlying molecular mechanism of lncRNAs in CG. In this study, we firstly isolated the primary cells from the tissues of CG and adjacent normal tissues, and found that UCA1 was up-regulated in the primary CG cells (pCGs). Then, we showed that knock out of UCA1 reduced the cell viability, inhibited the cell proliferation and restrained the migration potential and overexpression of UCA1 promoted that in pCGs. Furthermore, we demonstrated that UCA1 played its role via sponging of the miR-204 in pCGs. In addition, we illustrated that miR-204 exerted its function via targeting CYCLIN D2 (CCND2) 3'UTR at mRNA level in pCGs. Ultimately, we revealed the role and regulation of UCA1/miR-204/CCND2 regulatory axis in pCGs. In summary, our study, for the first time, revealed the role and underlying mechanism of an lncRNA UCA1 in CG, providing a potential biomarker and therapeutic target for human CG.

Association of metformin intake with bladder cancer risk and oncologic outcomes in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

BACKGROUND: Recent clinical trials indicated that metformin intake might play a protective role in the incidence and oncologic outcomes of various cancers. However, its protective effect on bladder cancer remains uncertain. METHODS: We performed a meta-analysis to investigate the association between metformin intake and bladder cancer risk as well as oncologic outcomes in diabetes mellitus (DM) patients. A comprehensive literature search was performed using PubMed, Embase, and the Cochrane Central Search Library in December 2017. Hazard ratio (HR) with 95% confidence interval (CI) was pooled. RESULTS: A total of 9 retrospective cohort studies with 1,270,179 patients were included. A meta-analysis revealed that metformin intake was associated with an increased recurrence-free survival (HR = 0.55, 95% confidence interval [CI] = 0.35-0.88; P = .01; I = 64%), improved progression-free survival (HR = 0.70, 95% CI = 0.51-0.96; P = .03; I = 33%), and prolonged cancer-specific survival (HR = 0.57, 95% CI = 0.40-0.81; P = .002; I = 0%). However, results demonstrated that metformin intake was not associated with a decreased incidence of bladder cancer (HR = 0.82, 95% CI = 0.61-1.09; P = .17; I = 85%) or an increased overall survival in bladder cancer patients (HR = 0.83, 95% CI = 0.47-1.44; P = .50; I = 64%). CONCLUSION: The present meta-analysis indicated that metformin intake could improve the prognosis of bladder cancer patients. Further prospective cohort studies and mechanistic studies are still required to determine the precise role of metformin in the initiation and progression of bladder cancer.

Association Between 12 Polymorphisms of VEGF/Hypoxia/Angiogenesis Pathway Genes and Risk of Urogenital Carcinomas: A Meta-Analysis Based on Case-Control Studies.

Objective: Previous studies indicated potential associations between polymorphisms in genes of VEGF/hypoxia/angiogenesis pathway and risk of urogenital carcinomas However, the results were controversial and inconclusive. Here, we conducted an in-depth meta-analysis to investigate the precise associations between polymorphisms in VEGF/hypoxia/angiogenesis related genes and risk of urogenital carcinomas. Methods: We searched PubMed, Web of Science, EMBASE, and Cochrane Library to identify all eligible publications. Pooled odds ratios (ORs) corresponding with the 95% confidence intervals (CIs) were calculated to evaluate their associations. Subgroup analysis was conducted to further ascertain such relationship and investigate sources of heterogeneity. Results: In the end, a total of 96 case-control studies fulfilled the inclusion criteria were enrolled for 12 polymorphisms in 4 VEGF/hypoxia/angiogenesis related genes. The pooled results showed eNOS-rs2070744 polymorphism conferred a significantly increased overall risk of urogenital carcinomas in allele, homozygote, and recessive models, respectively. In addition, eNOS-Intron 4a/b VNTR polymorphism was identified related to an increased risk of urogenital carcinomas in recessive model. And VEGF-rs699947 polymorphism was also identified an increased risk of renal cell carcinoma (RCC) in allelic, heterozygote, dominant, homozygote, and recessive models. Conclusion: To conclude, eNOS-rs2070744 and eNOS-Intron 4a/b VNTR polymorphisms are risk factors for urogenital carcinomas. VEGF-rs699947 polymorphism was also identified as an increased risk factor for renal carcinoma.

High Expression of Long Noncoding RNA MALAT1 Indicates a Poor Prognosis and Promotes Clinical Progression and Metastasis in Bladder Cancer.

BACKGROUND: Recent studies have demonstrated that the expression of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes cancer cell proliferation, invasion, and metastasis in many tumor types, but the association between bladder cancer and MALAT1 remains unknown. MATERIALS: The expression of MALAT1 was tested by in situ hybridization (ISH) in 120 bladder cancer specimens. The association between MALAT1 expression and clinicopathological features and prognosis of the patients with bladder cancer was analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the relationship between the expression of MALAT1 and progression and metastasis of bladder cancer. RESULTS: ISH showed that high MALAT1 expression was associated with advanced histological grade, high tumor stage, and positive lymph nodes. Kaplan-Meier survival analysis and Cox regression analysis indicated that high tumor stage, positive lymph nodes, and high MALAT1 expression were independent prognostic indicators for overall survival (OS) of patients with bladder cancer. qRT-PCR showed that the expression of MALAT1 in bladder cancer tissues was 2.85 times higher than those measured in adjacent normal tissues (P < .001). The expression of MALAT1 was 2.673 ± 0.254 in non-muscle-invasive bladder cancer and 2.987 ± 0.381 in muscle-invasive bladder cancer (P = .018). In bladder cancer specimens with positive lymph nodes, MALAT1 expression was 3.167 ± 0.297 versus 2.896 ± 0.329 in bladder cancer specimens with negative lymph nodes (P = .020). CONCLUSION: High MALAT1 expression could serve as an independent prognostic factor for OS of patients with bladder cancer and could be considered as a potential therapeutic target of bladder cancer.

Localized chromophobe renal cell carcinoma: preoperative imaging judgment and laparoscopic simple enucleation for treatment

ABSTRACT Objective: To evaluate the preoperative imaging manifestation and therapeutic effect of laparoscopic simple enucleation (SE) for localized chromophobe renal cell carcinoma (chRCC). Materials and Methods: Clinical data of 36 patients who underwent laparoscopic SE of localized chRCC at our institute were retrospectively analyzed. All patients underwent preoperative renal protocol CT (unenhanced, arterial, venous, and delayed images). CT scan characteristics were evaluated. After intraoperative occlusion of the renal artery, the tumor was free bluntly along the pseudocapsule and enucleated totally. The patients were followed up regularly after the operation. Results: Mean tumor diameter was 3.9±1.0 cm, 80% of tumors were homogeneous and all the tumors had complete pseudocapsule. The attenuation values were slightly lower than normal renal cortex and degree of enhancement of the tumors were significantly lower than normal renal cortex. Mean operation time was 104.3±18.2 min. Mean warm ischemia time (WIT) was 21.3±3.5 min. Mean blood loss was 78.6±25.4 mL. No positive surgical margin was identified. Mean postoperative hospital stay was 5.3±1.5 d. Hematuria occurred in 3 patients and all disappeared within 3 days. After a mean follow-up of 32.1±20.6 months, no patient had local recurrence or metastatic progression. Conclusion: Localized chRCCs have a great propensity for homogeneity and complete pseudocapsule. The attenuation values were slightly lower than normal renal cortex and small degree of enhancement. Laparoscopic SE is a safe and effective treatment for localized chRCC. The oncological results were satisfactory.