Perfusion drugs for non­muscle invasive bladder cancer (Review).

The high recurrence rate and poor prognosis of non-muscle invasive bladder cancer (BC) are challenges that need to be urgently addressed. Transurethral cystectomy for bladder tumors is often combined with bladder perfusion therapy, which can effectively reduce the recurrence and progression rates of BC. The present review integrated and analyzed currently available bladder perfusion drugs, mainly including chemotherapeutic agents, immunotherapeutic agents and other adjuvant perfusion drugs. Bacillus Calmette-Guerin (BCG) perfusion was the pioneering immunotherapy for early BC and still ranks high in the selection of perfusion drugs. However, BCG infusion has a high toxicity profile and has been shown to be ineffective in some patients. Due to the limitations of BCG, new bladder perfusion drugs are constantly being developed. Immunotherapeutic agents have opened a whole new chapter in the selection of therapeutic agents for bladder perfusion. The present review explored the mechanism of action, clinical dosage and adverse effects of a variety of bladder perfusion drugs currently in common use, described combined perfusion and compared the effects of certain drugs on BC.

Advances in tumor microenvironment and underlying molecular mechanisms of bladder cancer: a systematic review.

Bladder cancer is one of the most frequent malignant tumors of the urinary system. The prevalence of bladder cancer among men and women is roughly 5:2, and both its incidence and death have been rising steadily over the past few years. At the moment, metastasis and recurrence of advanced bladder cancer-which are believed to be connected to the malfunction of multigene and multilevel cell signaling network-remain the leading causes of bladder cancer-related death. The therapeutic treatment of bladder cancer will be greatly aided by the elucidation of these mechanisms. New concepts for the treatment of bladder cancer have been made possible by the advancement of research technologies and a number of new treatment options, including immunotherapy and targeted therapy. In this paper, we will extensively review the development of the tumor microenvironment and the possible molecular mechanisms of bladder cancer.

CHSY1 promotes CD8+ T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on CRISPR/Cas9 screening.

BACKGROUND: The most common site of metastasis in colorectal cancer (CRC) is the liver and liver metastases occur in more than 50% of patients during diagnosis or treatment. The occurrence of metastasis depends on a series of events known as the invasive-metastasis cascade. Currently, the underlying genes and pathways regulating metastasis initiation in the liver microenvironment are unknown. METHODS: We performed systematic CRISPR/Cas9 screening using an in vivo mouse model of CRC liver metastasis to identify key regulators of CRC metastasis. We present the full results of this screen,which included a list of genes that promote or repress CRC liver colonization. By silencing these genes individually, we found that chondroitin sulfate synthase 1 (CHSY1) may be involved in CRC metastasis. We verified the function of CHSY1 and its involvement in liver metastasis of CRC through in vivo and in vitro experiments. RESULT: The results of TCGA and CRISPR/Cas9 showed that CHSY1 was overexpressed in CRC primary and liver metastasis tissues and indicated a worse clinical prognosis. In vitro and in vivo experiments confirmed that CHSY1 facilitated the liver metastasis of CRC and CHSY1 induced CD8+ T cell exhaustion and upregulated PD-L1 expression. The metabolomic analysis indicated that CHSY1 promoted CD8+ T cell exhaustion by activating the succinate metabolism pathway leading to liver metastasis of CRC. Artemisinin as a CHSY1 inhibitor reduced liver metastasis and enhanced the effect of anti-PD1 in CRC. PLGA-loaded Artemisinin and ICG probe reduced liver metastasis and increased the efficiency of anti-PD1 treatment in CRC. CONCLUSION: CHSY1 could promote CD8+ T cell exhaustion through activation of the succinate metabolic and PI3K/AKT/HIF1A pathway, leading to CRC liver metastasis. The combination of CHSY1 knockdown and anti-PD1 contributes to synergistic resistance to CRC liver metastasis. Artemisinin significantly inhibits CHSY1 activity and in combination with anti-PD1 could synergistically treat CRC liver metastases. This study provides new targets and specific strategies for the treatment of CRC liver metastases, bringing new hope and benefits to patients.

Extracellular RNA in melanoma: Advances, challenges, and opportunities.

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%-3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According to previous studies, extracellular RNAs (exRNAs) have been implicated in tumorigenesis and spread of melanoma. They can influence the proliferation, invasion and metastasis of melanoma by controlling the expression of target genes and can also influence tumor progression by participating in signal transduction mechanisms. Therefore, understanding the relationship between exRNA and malignant melanoma and targeting therapy is of positive significance for its prevention and treatment. In this review, we did an analysis of extracellular vesicles of melanoma which focused on the role of exRNAs (lncRNAs, miRNAs, and mRNAs) and identifies several potential therapeutic targets. In addition, we discuss the typical signaling pathways involved in exRNAs, advances in exRNA detection and how they affect the tumor immune microenvironment in melanoma.

From Immunogen to COVID-19 vaccines: Prospects for the post-pandemic era.

The COVID-19 pandemic has affected millions of people and posed an unprecedented burden on healthcare systems and economies worldwide since the outbreak of the COVID-19. A considerable number of nations have investigated COVID-19 and proposed a series of prevention and treatment strategies thus far. The pandemic prevention strategies implemented in China have suggested that the spread of COVID-19 can be effectively reduced by restricting large-scale gathering, developing community-scale nucleic acid testing, and conducting epidemiological investigations, whereas sporadic cases have always been identified in numerous places. Currently, there is still no decisive therapy for COVID-19 or related complications. The development of COVID-19 vaccines has raised the hope for mitigating this pandemic based on the intercross immunity induced by COVID-19. Thus far, several types of COVID-19 vaccines have been developed and released to into financial markets. From the perspective of vaccine use in globe, COVID-19 vaccines are beneficial to mitigate the pandemic, whereas the relative adverse events have been reported progressively. This is a review about the development, challenges and prospects of COVID-19 vaccines, and it can provide more insights into all aspects of the vaccines.

Immunotherapy: Review of the Existing Evidence and Challenges in Breast Cancer.

Breast cancer (BC) is a representative malignant tumor that affects women across the world, and it is the main cause of cancer-related deaths in women. Although a large number of treatment methods have been developed for BC in recent years, the results are sometimes unsatisfying. In recent years, treatments of BC have been expanded with immunotherapy. In our article, we list some tumor markers related to immunotherapy for BC. Moreover, we introduce the existing relatively mature immunotherapy and the markers' pathogenesis are involved. The combination of immunotherapy and other therapies for BC are introduced in detail, including the combination of immunotherapy and chemotherapy, the combined use of immunosuppressants and chemotherapy drugs, immunotherapy and molecular targeted therapy. We summarize the clinical effects of these methods. In addition, this paper also makes a preliminary exploration of the combination of immunotherapy, radiotherapy, and nanotechnology for BC.

Diagnostic role of plasma ORM2 in differentiating prostate cancer from benign prostatic hyperplasia.

PURPOSE: Markers are needed to increase the diagnostic accuracy of prostate-specific antigen (PSA) in prostate cancer (PCa) screening. Mounting evidence has shown that plasma proteins can be hopeful biomarkers for cancer diagnosis. METHODS: Tandem mass tag (TMT)-based proteomics and parallel reaction monitoring (PRM) analysis were used to screen the differential proteins and further validated in other independent studies (n = 539). Receiver-operating characteristic (ROC), decision curves and nomograms were applied to assess the diagnostic accuracy of biomarkers. RESULTS: Three candidate proteins (DBP, LCAT and ORM2) were preliminarily screened. Subsequent validation studies revealed significant upregulation of ORM2 in PCa patients across other independent cohorts. ORM2 yielded excellent discriminative power for PCa from benign prostatic hyperplasia (BPH) patients (AUC = 0.861 and 0.814 in validation phases 2a and 2b, respectively). Importantly, the combination of ORM2 and PSA gave better predictive accuracy than PSA alone. We incorporated age, PSA and ORM2 into a nomogram, which yielded C-index of 0.883 in validation phase 2a. A similar C-index of 0.879 was obtained in external validation phase 2b. CONCLUSIONS: In summary, our study suggests that ORM2 could be treated as a complementary biomarker for PSA in distinguishing PCa from BPH.

LncRNA SNHG1 Facilitates Tumor Proliferation and Represses Apoptosis by Regulating PPARγ Ubiquitination in Bladder Cancer.

BACKGROUND: Long noncoding RNAs regulate various biological effects in the progression of cancers. We found that the expression of SNHG1 was significantly up-regulated in bladder cancer after analyzing data obtained from TCGA and GEO. However, the potential role of SNHG1 remains to be investigated in bladder cancer. It was validated that SNHG1 was overexpressed in bladder cancer tissues detected by qRT-PCR and FISH, which was also associated with poor clinical outcome. Additionally, SNHG1 was verified to facilitate tumor proliferation and repress apoptosis in vitro and in vivo. RESULTS: SNHG1 could act as a competitive endogenous RNA and decrease the expression of murine double minute 2 (MDM2) by sponging microRNA-9-3p. Furthermore, MDM2 induced ubiquitination and degradation of PPARγ that contributed to the development of bladder cancer. CONCLUSIONS: the study elucidated that SNHG1 played an important role in bladder cancer and provided a potential therapeutic target for bladder cancer.

Comprehensive FGFR3 alteration-related transcriptomic characterization is involved in immune infiltration and correlated with prognosis and immunotherapy response of bladder cancer.

Background: Bladder cancer (BC) threatens the health of human beings worldwide because of its high recurrence rate and mortality. As an actionable biomarker, fibroblast growth factor receptor 3 (FGFR3) alterations have been revealed as a vital biomarker and associated with favorable outcomes in BC. However, the comprehensive relationship between the FGFR3 alteration associated gene expression profile and the prognosis of BC remains ambiguous. Materials and Methods: Genomic alteration profile, gene expression data, and related clinical information of BC patients were downloaded from The Cancer Genomics database (TCGA), as a training cohort. Subsequently, the Weighted Gene Co-expression Network Analysis (WGCNA) was conducted to identify the hub modules correlated with FGFR3 alteration. The univariate, multivariate, and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to obtain an FGFR3 alteration-related gene (FARG) prognostic signature and FARG-based nomogram. The receiver operating characteristic (ROC) curve analysis was used for evaluation of the ability of prognosis prediction. The FARG signature was validated in four independent datasets, namely, GSE13507, GSE31684, GSE32548, and GSE48075, from Gene Expression Omnibus (GEO). Then, clinical feature association analysis, functional enrichment, genomic alteration enrichment, and tumor environment analysis were conducted to reveal differential clinical and molecular characterizations in different risk groups. Lastly, the treatment response was evaluated in the immunotherapy-related dataset of the IMvigor210 cohort and the frontline chemotherapy dataset of GSE48276, and the chemo-drug sensitivity was estimated via Genomics of Drug Sensitivity in Cancer (GDSC). Results: There were a total of eleven genes (CERCAM, TPST1, OSBPL10, EMP1, CYTH3, NCRNA00201, PCDH10, GAP43, COLQ, DGKB, and SETBP1) identified in the FARG signature, which divided BC patients from the TCGA cohort into high- and low-risk groups. The Kaplan-Meier curve analysis demonstrated that BC patients in the low-risk group have superior overall survival (OS) than those in the high-risk group (median OS: 27.06 months vs. 104.65 months, p < 0.0001). Moreover, the FARG signature not only showed a good performance in prognosis prediction, but also could distinguish patients with different neoplasm disease stages, notably whether patients presented with muscle invasive phenotype. Compared to clinicopathological features, the FARG signature was found to be the only independent prognostic factor, and subsequently, a FARG-based prognostic nomogram was constructed with better ability of prognosis prediction, indicated by area under ROC curve (AUC) values for 1-, 3-, and 5-year OS of 0.69, 0.71, and 0.79, respectively. Underlying the FARG signature, multiple kinds of metabolism- and immune-related signaling pathways were enriched. Genomic alteration enrichment further identified that FGFR3 alterations, especially c.746C>G (p.Ser249Cys), were more prevalent in the low-risk group. Additionally, FARG score was positively correlated with ESTIMATE and TIDE scores, and the low-risk group had abundant enrichment of plasma B cells, CD8+ T cells, CD4+ naive T cells, and helper follicular T cells, implying that patients in the low-risk group were likely to make significant responses to immunotherapy, which was further supported by the analysis in the IMvigor210 cohort as there was a significantly higher response rate among patients with lower FARG scores. The analysis of the GDSC database finally demonstrated that low-risk samples were more sensitive to methotrexate and tipifarnib, whereas those in the high-risk group had higher sensitivities in cisplatin, docetaxel, and paclitaxel, instead. Conclusion: The novel established FARG signature based on a comprehensive FGFR3 alteration-related transcriptomic profile performed well in prognosis prediction and was also correlated with immunotherapy and chemotherapy treatment responses, which had great potential in future clinical applications.

RUNX3-mediated circDYRK1A inhibits glutamine metabolism in gastric cancer by up-regulating microRNA-889-3p-dependent FBXO4.

BACKGROUND: Targeting glutamine metabolism is previously indicated as a potential and attractive strategy for gastric cancer (GC) therapy. However, the underlying mechanisms responsible for the modification of glutamine metabolism in GC cells have not been fully elucidated. Accordingly, the current study sought to investigate the physiological mechanisms of RUNX3-mediated circDYRK1A in glutamine metabolism of GC. METHODS: Firstly, GC tissues and adjacent normal tissues were obtained from 50 GC patients to determine circDYRK1A expression in GC tissues. Next, the binding affinity among RUNX3, circDYRK1A, miR-889-3p, and FBXO4 was detected to clarify the mechanistic basis. Moreover, GC cells were subjected to ectopic expression and knockdown manipulations of circDYRK1A, miR-889-3p, and/or FBXO4 to assay GC cell malignant phenotypes, levels of glutamine, glutamic acid, and α-KG in cell supernatant and glutamine metabolism-related proteins (GLS and GDH). Finally, nude mice were xenografted with GC cells to explore the in vivo effects of circDYRK1A on the tumorigenicity and apoptosis. RESULTS: circDYRK1A was found to be poorly expressed in GC tissues. RUNX3 was validated to bind to the circDYRK1A promoter, and circDYRK1A functioned as a miR-889-3p sponge to up-regulate FBXO4 expression. Moreover, RUNX3-upregulated circDYRK1A reduced levels of glutamine, glutamic acid, and α-KG, and protein levels of GLS and GDH, and further diminished malignant phenotypes in vitro. Furthermore, in vivo experimentation substantiated that circDYRK1A inhibited the tumorigenicity and augmented the apoptosis in GC. CONCLUSION: In conclusion, these findings highlighted the significance and mechanism of RUNX3-mediated circDYRK1A in suppressing glutamine metabolism in GC via the miR-889-3p/FBXO4 axis.

Identifying a Novel Defined Pyroptosis-Associated Long Noncoding RNA Signature Contributes to Predicting Prognosis and Tumor Microenvironment of Bladder Cancer.

Background: Bladder cancer (BLCA) is a common malignant tumor of the urinary tract, which is the sixth most common cancer among men. Numerous studies suggested that pyroptosis and long noncoding RNAs (lncRNAs) played an essential role in the development of cancers. However, the role of pyroptosis-related lncRNAs in BLCA and their prognostic value are still unclear. Methods: In this study, we constructed a signature model through least absolute shrinkage and selection operator (LASSO) Cox regression analysis and Cox univariate analysis based on The Cancer Genome Atlas (TCGA) database. The expression of 12 pyroptosis-related lncRNAs was also confirmed by qRT-PCR in BLCA cell lines. TIMER, XCELL, QUANTISEQ, MCPCOUNTER, EPIC, and CIBERSORT R script were applied to quantify the relative proportions of infiltrating immune cells. Correlation coefficients were computed by Spearman analyses. The Kaplan-Meier method, Cox regression model, and log-rank tests were used to evaluate the prognostic value. The R package of pRRophetic was used to predict IC50 of common chemotherapeutic agents. Results: A total of 12 pyroptosis-related lncRNAs with great prognosis value were identified. The expression was investigated by qRT-PCR in four BLCA cell lines. Then, 126 cases were identified as high-risk group, and 277 cases were identified as low-risk group based on the cutoff point. Patients in the low-risk group showed a significant survival advantage. Furthermore, we found that clinical features were significantly related to the risk score. As well, based on the C-index values, a nomogram was constructed. The gene set enrichment analysis (GSEA) results showed that mitogen-activated protein kinase (MAPK) signaling, transforming growth factor (TGF)-ß signaling, and WNT signaling were with important significance in the high-risk group. Moreover, we found that riskscore was positively correlated with M0 macrophages and M2 macrophages. Conclusions: In conclusion, our study indicated that pyroptosis is closely connected to BLCA. The riskscore generated from the expression of 12 pyroptosis-related lncRNAs was evaluated by various clinical features including survival status, tumor microenvironment, clinicopathological characteristic, and chemotherapy. It may offer a significant basis for future studies.

Exosomal MicroRNA-9-3p Secreted from BMSCs Downregulates ESM1 to Suppress the Development of Bladder Cancer.

Exosomes, carriers to transfer endogenous molecules, derived from bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to play a role in the progression of bladder cancer. Here we aimed to test the functional mechanism of microRNA-9-3p (miR-9-3p)-containing exosomes derived from BMSCs in bladder cancer. BMSCs were cocultured with bladder cancer cells, and exosomes secreted from BMSCs were identified. Next, the expression of miR-9-3p and endothelial cell-specific molecule 1 (ESM1) in bladder cancer tissues and cells was determined. Then effects of miR-9-3p and ESM1 via BMSC-derived exosomes on bladder cancer cell viability, migration, invasion, and apoptosis were determined by loss- and gain-of-function experiments and on in vivo tumor growth, and metastasis was assessed in nude mice. miR-9-3p expression was decreased and ESM1 was increased in bladder cancer. BMSCs inhibited bladder cancer cell viability, migration, and invasion, and induced apoptosis, whereas the addition of exosome secretion inhibitor GW4869 achieved the opposite effects. Moreover, exosomal miR-9-3p upregulation or ESM1 silencing suppressed bladder cancer cell viability, migration, and invasion; induced cell apoptosis; and inhibited in vivo tumor growth and metastasis. Taken together, BMSC-derived exosomal miR-9-3p suppressed the progression of bladder cancer through ESM1 downregulation, offering a potential novel therapeutic target for bladder cancer therapy.

A new strategy for the treatment of sorafenib-refractory metastatic renal cell carcinoma in China: combination with intermittent chemotherapy.

BACKGROUND: This study assesses the clinical safety and efficacy of Gemcitabine and S-1 combination chemotherapy in sorafenib-refractory metastatic renal cell carcinoma (RCC) patients. METHODS: The baseline characteristics and survival outcomes of 19 patients suffering from metastatic and progressive sorafenib-refractory RCC were retrospectively collected and analyzed from January 2010 to April 2014. Patients were treated by combining Gemcitabine (1,000 mg/m2, day 1 and day 8 of every cycle of 21 days) and S-1 (40 mg/m2, twice a day for 14 days, followed by the rest period of 7 days), with a continual treatment of sorafenib 400 mg twice a day in a cycle of 28 days. RESULTS: After combination chemotherapy, the disease control rate was 68.4%. Among them, 6 patients (31.6%) had progressive disease (PD), 5 patients (26.3%) had stable disease (SD) and 8 patients (42.1%) had partial response (PR). The median time to progression (TTP) was 6.3 months (range, 2.0-32.7 months), and the median overall survival (OS) was 19.7 months (range, 5.7-45.0 months). In the survival analysis, comparing PD group, disease control (PR + SD) group showed an obviously longer TTP (median TTP: 9.5 vs. 2.0 months, 95% CI, 7.7-11.3 months, P<0.001) and OS (median OS: 21.0 vs. 8.3 months, 95% CI, 14.5-24.9 months, P<0.001). In univariate and multivariate analysis, TTP and OS were significantly associated with disease control condition. Side-effects were found in all patients at different degree, but only 3 patients suffered grade 3/4 toxicities (15.8%). No death related to treatment was observed. CONCLUSIONS: The combination chemotherapy could be a promising treatment option for advanced metastatic RCC (mRCC) patients after sorafenib refractory.

Clinical characteristics and genetic testing of an atypical familial von Hippel-Lindauzon renal cell carcinoma.

BACKGROUND: A case of familial bilateral von Hippel-Lindauzon (VHL) renal cell carcinoma (RCC) was retrospectively reviewed and the etiological diagnosis was based on clinical characteristics and genetic testing. METHODS: The clinical manifestations and imaging data were gained from the hospital information system (HIS). Peripheral blood samples were collected and genomic DNA and RNA were extracted. Additionally, mutations of VHL gene such as tiny insertion and deletion of base, point mutation and large deletion of gene were then detected and analyzed by DNA sequencing, real-time quantitative PCR and RT-PCR. RESULTS: Real-time quantitative PCR and RT-PCR products sequencing showed that the number of VHL gene copies in peripheral blood of the patient was decreased, and pathological germline mutation was detected caused by single copy deletion of exon 2 of VHL gene. The patient was diagnosed as atypical VHL RCC according to clinical manifestations and genetic testing outcomes. CONCLUSIONS: VHL RCC can be diagnosed based on its clinical manifestations and genetic testing results.

Docetaxel Combined With Cisplatin for Metastatic Extramammary Paget Disease.

INTRODUCTION: Metastatic extramammary Paget disease (EMPD) as a rare intraepithelial carcinoma is fatal. However, no standardized chemotherapy has been established. We provided docetaxel combined with cisplatin to EMPD patients. PATIENTS AND METHODS: A total of 8 patients with metastatic EMPD were included in this study between July 2010 and July 2015 (mean age, 64.4 years); they underwent a mean of 9.4 cycles of chemotherapy. All the patients were treated with chemotherapy (docetaxel 60 mg/m2 on day 1; cisplatin 25 mg/m2 on days 1-3) as first-line treatment for > 6 cycle (at least 21 days per cycle). Data on tumor response, time to progression, overall survival, and adverse events were collected. RESULTS: After 2 cycles of chemotherapy, 4 patients experienced partial remission and 4 stable disease. The mean overall survival was 28.9 months, and the mean progression-free survival was 9.9 months. CONCLUSION: Docetaxel combined with cisplatin might be a treatment option for metastatic EMPD, with high disease control rate and good overall survival.

Association of N-acetyltransferase 1 polymorphism and bladder cancer risk: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Individual studies of the association between N-acetyltransferase 1 (NAT1)*10 allele and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of any such relationship, we performed this systemic review and updated meta-analysis based on 17 publications. METHODS: A total of 17 studies were investigated with 4,322 bladder cancer cases and 4,944 controls. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Subgroup analyses were conducted based on ethnicity, sex, source of controls and detecting methods. Then trial sequential analysis was performed to evaluate whether the evidence of the results was sufficient and reduce the risk of type I error. RESULTS: There was no association between NAT1*10 allele and bladder cancer risk in a random-effects model (OR = 0.96, 95% CI, 0.84-1.10) or in a fixed-effects model (OR = 0.95, 95% CI, 0.87-1.03). In addition, no significantly increased risk of bladder cancer was found in any other subgroup analysis. Then, trial sequential analyses demonstrated that the results of our study need to be further verified. CONCLUSIONS: Despite its limitations, the results of the present meta-analysis suggested that there was no association between NAT1*10 allele and bladder cancer risk. More importantly, our findings need to be further validated regarding whether being without the NAT1*10 allele could in the future be shown to be a potential marker for the risk of bladder cancer.

Comparison between transrectal and transperineal prostate biopsy for detection of prostate cancer: a meta-analysis and trial sequential analysis.

To systematically assess the efficacy and complications of transrectal (TR) versus transperineal (TP) prostate biopsy in the detection of prostate cancer (PCa). A meta-analysis was performed by searching the databases Pubmed, Embase and Web of science for the relevant available studies until September 1st, 2016, and thirteen studies met the inclusion criteria. The pooled odds ratios with 95% confidence intervals were calculated to evaluate the differences of TR and TP groups in PCa detection rate. Then, trial sequential analysis was performed to reduce the risk of type I error and estimated whether the evidence of the results was reliable. Overall, this meta-analysis included a total of 4280 patients, who had been accrued between April 2000 and Aug 2014 and randomly divided into TR group and TP group. Prostate biopsies included sextant, extensive and saturation biopsy procedures. Patients who received TP prostate biopsy had no significant improvement in PCa detection rate, comparing TR group. Moreover, when comparing TR and TP studies, no significant difference was found in abnormal DRE findings, serum PSA level measurement, Gleason score, prostate volume. Besides, this meta-analysis showed no obvious differences between these two groups in terms of relevant complications. Therefore, this meta-analysis revealed that no significant differences were found in PCa detection rate between TP and TR approaches for prostate biopsy. However, with regard to pain relief and additional anesthesia, TR prostate needle biopsy was relatively preferable, compared to TP prostate biopsy.

Association between manganese superoxide dismutase (MnSOD) polymorphism and prostate cancer susceptibility: a meta-analysis.

BACKGROUND: Previous studies have investigated the relationship between manganese superoxide dismutase (MnSOD) Val16Ala polymorphism and prostate cancer susceptibility, but the results have remained controversial. This meta-analysis was therefore performed to clarify this association. METHODS: The databases PubMed, Embase and Web of Science were searched for relevant available studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Trial sequential analysis was used to reduce the risk of type I error and estimate whether the evidence of the results was sufficient. RESULTS: Overall, a significant increased risk of prostate cancer was associated with MnSOD Val16Ala polymorphism for the heterozygote model (OR = 1.14; 95% CI, 1.05-1.24), homozygote model (OR = 1.18; 95% CI, 1.02-1.36), dominant model (OR = 1.24; 95% CI, 1.07-1.44) and recessive model (OR = 1.10; 95% CI, 0.96-1.24). In the subgroup analysis by genotyping method, the results were statistically significant for the TaqMan and PCR-RFLP methods. In addition, when stratified by sample size, statistically significant increased risks were found among both large samples and small samples. Furthermore, when stratified by source of control, significant results were detected in both population-based controls and hospital-based controls. By trial sequential analyses, these findings in the current study were shown to be based on sufficient evidence. CONCLUSIONS: This meta-analysis indicated that the Ala allele of the MnSOD gene polymorphism increases prostate cancer susceptibility.