The influence of prostate volume on pathological outcomes after radical prostatectomy: A single-center retrospective study.

Currently, the association between prostate volume (PV) or prostate weight with pathological outcomes in patients with prostate cancer (PCa) is not well understood. This study aimed to explore whether PV can predict the adverse pathological outcomes of PCa patients after radical prostatectomy (RP). A total of 1063 men with confirmed localized PCa who underwent RP at the First Affiliated Hospital of Zhejiang University from January 2014 to April 2019 were retrospectively analyzed. Patients were assigned into small, medium and large groups based on the PV. The analysis of variance, χ2 test or Student t test was performed to compare differences among groups. Univariate and multivariate analyses were performed to identify significant predictors of pathological outcomes upgrading. Among the 1063 cases, approximately 35.0% had an upgrade of postoperative pathology. Compared with the small prostate group, more patients in the large prostate group achieved a Gleason score (GS) 6 and International Society of Urological Pathology (ISUP) grade 1 of postoperative pathological findings, clinical cT1c and cT2a stages and pathological pT2a and pT2b stages; the incidence of positive surgical margins and extraprostatic extension was relatively low (all P < .001). In multiple logistic regression, PV served as a significant predictor of any Gleason score upgrading (GSU) (odds ratio [OR] 0.988, 95% confidence interval [CI] 0.978-0.998), major GSU (OR 0.980, 95% CI 0.965-0.995) and any ISUP grade group upgrading (GGU) (OR 0.989, 95% CI 0.979-0.999). This study shows that PV can predict adverse pathological outcomes in PCa patients after radical prostatectomy. Pca patients with smaller prostate volume tend to have the high-grade disease at postoperative pathology as well as pathological outcome upgrading.

Expression and Prognostic Value of Chromobox Family Proteins in Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) is one of the most common human malignant tumors worldwide. Chromobox (CBX) family proteins are significant components of epigenetic regulatory complexes. It is reported that CBXs play critical roles in the oncogenesis and development of various tumors. Nonetheless, their functions and specific roles in EC remain vague and obscure. METHODS AND MATERIALS: We used multiple bioinformatics tools, including Oncomine, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), UALCAN, Kaplan-Meier plotter, cBioPortal, Metascape, TIMER2 and TISIDB, to investigate the expression profile, gene alterations and prognostic roles of CBX family proteins, as well as their association with clinicopathologic parameters, immune cells and immune regulators. In addition, RT-qPCR, Western blot, CCK8, colony formation, wound healing and transwell assays were performed to investigate the biological functions of CBX3 in EC cells. RESULTS: CBX3 and CBX5 were overexpressed in EC compared to normal tissues. Survival analysis revealed that high expression of CBX1 predicted worse disease-free survival (DFS) in EC patients. Functionally, CBXs might participate in mismatch repair, spliceosome, cell cycle, the Fanconi anemia pathway, tight junction, the mRNA surveillance pathway and the Hippo signaling pathway in EC development. Furthermore, CBXs were related to distinct immune cells infiltration and immune regulators. Additionally, depletion of CBX3 inhibited the proliferation, migration and invasion abilities of EC cells. CONCLUSIONS: Our study comprehensively investigated the expression pattern, prognostic value, and gene alterations of CBXs in EC, as well as their relationships with clinicopathologic variables, immune cells infiltration and immune regulators. These results suggested that CBX family proteins, especially CBX3, might be potential biomarkers in the progression of EC.

FTO promotes clear cell renal cell carcinoma progression via upregulation of PDK1 through an m6A dependent pathway.

FTO, as an m6A mRNA demethylase, is involved in various cancers. However, the role of FTO in clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we discovered FTO is upregulated in ccRCC. Functionally, knockdown of FTO significantly impairs the proliferation and migration ability of ccRCC cells. Mechanistically, our data suggest FTO promotes the proliferation and migration of ccRCC through preventing degradation of PDK1 mRNA induced by YTHDF2 in an m6A-dependent mechanism. Overall, our results identify the protumorigenic role of FTO through the m6A/YTHDF2/PDK1 pathway, which could be a promising therapeutic target for ccRCC.

SMAD3 and FTO are involved in miR-5581-3p-mediated inhibition of cell migration and proliferation in bladder cancer.

Previous research evidence suggests that microRNAs (miRNAs) play an indispensable role in onset and progression of bladder cancer (BCa). Here, we explored the functions and mechanisms of miR-5581-3p in BCa. miR-5581-3p, as a tumor suppressor in BCa, was detected at a lower expression level in BCa tissue and cells in contrast with the non-malignant bladder tissue and cells. Over-expression of miR-5581-3p remarkably dampened the migration and proliferation of BCa in vitro and in vivo. SMAD3 and FTO were identified as the direct targets of miR-5581-3p by online databases prediction and mRNA-seq, which were further verified. SMAD3 as a star molecule in modulating EMT progress of BCa had been formulated in former studies. Meanwhile, FTO proved as an N6-methyladenosine (m6A) demethylase in decreasing m6A modification was confirmed to regulate the migration and proliferation in BCa. In addition, we conducted rescue experiments and confirmed overexpressing miR-5581-3p partially rescued the effects of the overexpressing SMAD3 and FTO in BCa cells. In conclusion, our studies exhibit that miR-5581-3p is a novel tumor inhibitor of BCa.

SYT7 plays a role in promoting thyroid cancer by mediating HMGB3 ubiquitination.

Thyroid cancer is one of the most common endocrine malignancies. It is necessary to discover more effective molecular targets for the treatment of thyroid cancer. The results of immunohistochemical staining, qPCR and Western blot indicated that the expression of SYT7 in thyroid cancer tissues and cells was higher than that in paracarcinoma tissues and normal thyroid cells. Through cell function testing experiments, it was found that SYT7 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis, while SYT7 overexpression had the opposite effect. Similarly, SYT7 downregulation also suppressed tumor growth in vivo. HMGB3 was confirmed to be the downstream gene of SYT7 by GeneChip and Ingenuity Pathway Analysis. Besides, through UbiBrowser database predictions and Co-IP assays, we found that SYT7 interacted with BRCA1 to inhibit HMGB3 ubiquitination and thus upregulated the protein level of HMGB3. Similar to SYT7, HMGB3 was significantly upregulated in thyroid cancer. HMGB3 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis. Furthermore, HMGB3 knockdown restored the promotion of cell proliferation and migration caused by SYT7 overexpression. SYT7 and HMGB3 were upregulated in thyroid cancer, and SYT7 regulated the expression of HMGB3 through BRCA1-mediated ubiquitination of HMGB3 to promote thyroid cancer progression.

circKDM4C enhances bladder cancer invasion and metastasis through miR-200bc-3p/ZEB1 axis.

Circular RNAs (circRNAs) play essential roles in human bladder cancer (BCa) development, however, unusual expression patterns and functional dysfunction of circRNAs in BCa have not been evaluated. In this study, we validated that circKDM4C (hsa_circ_0001839), derived from the KDM4C gene, is elevated in BCa cell lines as well as tissues. Functionally, overexpression of circKDM4C significantly enhances, and silencing of circKDM4C suppresses migration and invasion capabilities of BCa cells. Mechanistically, circKDM4C can directly interact with miR-200b-3p and miR-200c-3p as a miRNA sponge, which enhances the expression of ZEB1 and promotes mesenchymal phenotype. Conclusively, our findings indicate that circKDM4C may act as a pro-oncogenic factor in BCa invasion and metastasis via the circKDM4C/miR-200bc-3p/ZEB1 axis, which is a potential biomarker or therapeutic target for bladder cancer.

MicroRNA-501-3p inhibits the proliferation of kidney cancer cells by targeting WTAP.

BACKGROUND: Emerging evidence suggests that miR-501-3p plays an important role in the pathogenesis and progression of various carcinomas. However, its role and underlying mechanisms in renal cell carcinoma (RCC) remain to be elucidated. METHODS: Quantitative RT-PCR, western blot, and bioinformatics methods were used to evaluate the expression of miR-501-3p and Wilms' tumor 1-associating protein (WTAP) in RCC cell lines and clinical tissues. The effects of miR-501-3p on the proliferation of RCC cells were investigated using flow cytometric, colony formation, and CCK8 assays. The target gene of miR-501-3p was confirmed by western blotting, qRT-PCR, and dual-luciferase reporter assays. The levels of RNA methylation with N6-methyladenosine (m6 A) following miR-501-3p overexpression or knockdown of its target gene were quantified using a dot-blot assay. RESULTS: miR-501-3p expression was significantly downregulated in human RCC cell lines and tissues. In contrast, its overexpression markedly inhibited cancer cell proliferation in vitro by inducing G1 phase arrest. Moreover, WTAP was verified as a direct target gene of miR-501-3p. WTAP gene knockdown alone efficiently produced the same cancer-inhibiting effects as miR-501-3p overexpression, with the level of m6 A in RCC cells being decreased under both scenarios. The intermolecular interaction between miR-501-3p and WTAP was further substantiated by rescue experiments. CONCLUSION: RCC progression is regulated via the miR-501-3p/WTAP/CDK2 axis and is inhibited by the overexpression of miR-501-3p.

Conditional survival of metastatic clear cell renal cell carcinoma: How prognosis evolves after cytoreductive surgery of primary tumor.

INTRODUCTION: Cytoreductive surgery is one of the recommended treatments for metastatic renal cell carcinoma, while the prognostic information of these patients treated with cytoreductive surgery is limited. In this study, we aimed to investigate the survival profiles based on conditional survival (CS) estimates in metastatic clear cell renal cell carcinoma (mccRCC) patients treated with cytoreductive surgery of primary tumor. METHODS AND MATERIALS: We identified and extracted mccRCC patients from the Surveillance, Epidemiology, and End Results database. We used Kaplan-Meier method to perform CS analyses. A multivariate Cox regression model was applied to explore the changes of well-known prognostic factors. RESULTS: Conditional overall survival (COS) and conditional cancer-specific survival (CCSS) improved increasingly at all periods of survivorships compared to survival estimates at baseline in overall population of mccRCC. The 36-month COS improved by 3.3%-6.4% given per 12 additional months of survivorships and the CCSS improved significantly from 45.1% (95% CI 42.8-47.3) at 12 months to 67.1% (95% CI 62.0-71.7) at 60 months. Much more survival gain was observed in patients with advanced disease. Furthermore, the prognostic significance of age and pathological factors diminished and even disappeared in a long-term survivorship. CONCLUSIONS: Conditional overall survival and CCSS improved with time dynamically in mccRCC patients treated with cytoreductive surgery of primary tumor. Patients with advanced disease achieved significant survival gain and even could harvest a better prognosis given that the time of survivorship exceeds a certain period. Our findings could provide valuable and practical data for patient counseling and surveillance strategy making.

Comprehensive Analysis of Ferroptosis Regulators With Regard to PD-L1 and Immune Infiltration in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the tumor types with sensitivity to ferroptosis, and immunotherapy has emerged as a standard pillar for metastatic ccRCC treatment, while it remains largely obscure whether ferroptosis influences the tumor immune microenvironment in ccRCC. Based on available data in The Cancer Genome Atlas, divergent expression profiles of ferroptosis regulators were noted in ccRCC and normal tissues, and we also found that the ferroptosis regulators correlated with the PD-L1 expression. Two independent subtypes were determined by consensus clustering analysis according to the expression level of ferroptosis regulators in ccRCC. Cluster 1 showed lower histological tumor stage and grade, more favorable prognosis, and higher PD-L1 expression compared to cluster 2. CIBERSORT analysis revealed that cluster 2 harbored higher infiltrated levels of CD8+ T cell, Tregs, and T follicular helper cell, while cluster 1 more correlated with the monocyte, M1 macrophage, and M2 macrophage. Gene set enrichment analysis indicated that the ERBB signaling and JAK_STAT signaling pathways were significantly enriched in cluster 1. We subsequently identified CARS as the potentially key immune infiltration-related ferroptosis regulator, whose high expression showed dismal prognosis and was positively correlated with PD-L1 expression in ccRCC. We also verified the upregulation of CARS in ccRCC tissues and cell lines via qRT-PCR method. Additionally, a pan-cancer analysis demonstrated that CARS closely related to the expression of immune checkpoint-related genes (especially PD-L1) and an unfavorable prognosis in diverse cancer types. In summary, our study suggested the crucial role of ferroptosis in immune infiltration of ccRCC, and CARS is a potentially novel prognostic biomarker and potential target for cancer immunotherapy.

miR-665 inhibits epithelial-to-mesenchymal transition in bladder cancer via the SMAD3/SNAIL axis.

Emerging research indicates that miRNAs can regulate cancer progression by influencing molecular pathways. Here, we studied miR-665, part of the DLK1-DIO3 miRNA cluster, which is downregulated by upstream methylation in bladder cancer. MiR-665 overexpression significantly downregulated the expression of SMAD3, phospho-SMAD3, and SNAIL, reversed epithelial-mesenchymal transition progression, and inhibited the migration of bladder cancer cells. To predict potential targets of miR-665, we used online databases and subsequently determined that miR-665 binds directly to the 3' untranslated region of SMAD3. Moreover, silencing of SMAD3 with small interfering RNAs phenocopied the effect of miR-665 overexpression, and overexpression of SMAD3 restored miR-665-overexpression-induced metastasis. This study revealed the role of the miR-665/SMAD3/SNAIL axis in bladder cancer, as well as the potential of miR-665 as a promising therapeutic target.

Clinicopathological characteristics of androgen receptor splicing variant 7 (AR-V7) expression in patients with castration resistant prostate cancer: A systematic review and meta-analysis.

BACKGROUND:  Studies have shown that AR-V7 may be correlated with the poor prognosis of castration resistant prostate cancer (CRPC), however, clinicopathological characteristics of AR-V7 have not been fully elucidated. OBJECTIVE: This study aimed at evaluating the clinicopathological features of AR-V7 in CRPC patients. MATERIALS AND METHODS: To evaluate the clinicopathological features of AR-V7 in CRPC patients. A search of PubMed, Embase, and Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma, AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Twenty-four trials published by February 2020 were included in this study. RESULTS: The proportion of Gleason score ≥ 8 was found to be significantly higher in AR-V7-positive CRPC (69.5%) than negative (54.9%) (OR 1.68, 95% CI 1.25-2.25, p < 0.001), while the rates of T3/T4 stage (OR 1.16, 95% CI 0.60-2.24, p = 0.65) and N1 stage (OR 0.99, 95% CI 0.65-1.51, p = 0.96) were not statistically correlated with AR-V7 status. The AR-V7-positive patients exhibited a significantly higher proportion of any site metastasis (61.3% versus 35.0%; OR 2.19, 95% CI 1.57-3.05, p < 0.001) and bone metastasis (81.7% versus 69.0%; OR 1.97, 95% CI 1.44-2.69, p < 0.001), and a trend close to significance was expected in visceral metastasis (28.8% versus 22.1%; OR 1.29, 95% CI 0.96-1.74, p = 0.09). Incidences of pain in AR-V7-positive CRPC (54.6%) were significantly higher than in negative CRPC (28.1%; OR 4.23, 95% CI 2.52-7.10, p < 0.001), line with worse ECOG performance status (56.7% versus 35.0%, OR 2.18, 95% CI 1.51-3.16, P < 0.001). Limitations of the study include differences in sample sizes and designs, AR-V7 detection assays, as well as disease characteristics of the included studies. CONCLUSIONS: AR-V7 positivity is associated with a higher Gleason score, bone or any site metastasis, pain and worse ECOG performance scores in CRPC. However, it is not correlated with tumor stage or lymph node metastasis. More studies are needed to confirm these findings.

Prognostic Value of Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Tumor-associated macrophages (TAMs) are the major immune cells in tumor microenvironment. The prognostic significance of TAMs has been confirmed in various tumors. However, whether TAMs can be prognostic factors in clear cell renal cell carcinoma (ccRCC) is unclear. In this study, we aimed to clarify the prognostic value of TAMs in ccRCC. METHODS: We searched PubMed, Embase, and the Web of Science for relevant published studies before December 19, 2020. Evidence from enrolled studies were pooled and analyzed by a meta-analysis. Hazard ratios (HRs) and odd ratios (ORs) with 95% confidence intervals (CIs) were computed to evaluate the pooled results. RESULTS: Both of high CD68+ TAMs and M2-TAMs were risk factors for poor prognosis in ccRCC patients. The pooled HRs indicated that elevated CD68+ TAMs correlated with poor OS and PFS (HR: 3.97, 95% CI 1.39-11.39; HR: 5.73, 95% CI 2.36-13.90, respectively). For M2-TAMs, the pooled results showed ccRCC patients with high M2-TAMs suffered a worse OS and shorter PFS, with HR 1.32 (95% CI 1.16-1.50) and 1.40 (95% CI 1.14-1.72), respectively. Also, high density of TAMs was associated with advanced clinicopathological features in ccRCC. CONCLUSIONS: TAMs could be potential biomarkers for prognosis and novel targets for immunotherapy in ccRCC. Further researches are warranted to validate our results.

Effects of fluorescent light cystoscopy in non-muscle-invasive bladder cancer: A systematic review and meta-analysis.

BACKGROUND: The benefits of fluorescent light (FL) cystoscopy with 5-aminolevulinic acid (5-ALA) or hexaminolevulinate (HAL) in non-muscle-invasive bladder cancer (NMIBC) have been mentioned in many trials. Meanwhile, several problems need to be addressed such as the rate of residual disease following these procedures. OBJECTIVE: To assess the effects of FL cystoscopy compared with white light (WL) cystoscopy on the rate of residual Ta, T1, and carcinoma in situ (CIS) tumors, recurrence-free survival (RFS) and progression-free survival (PFS). METHODS: A search in the databases PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Biology Medicine (CBM) was undertaken. Studies were included if their outcomes included the residual tumor rate, PFS or RFS. The data was analyzed by REVMAN 5.3 and STATA 14.0. RESULTS: The residual tumor rate of the FL group was lower than that of the WL group (relative risk [RR] 0.42; 95 % confidence interval [CI] 0.26-0.80; P = 0.007), which was consistent with the residual Ta rate (RR 0.44; 95 % CI 0.28-0.69; P = 0.0004), the residual T1 rate (RR 0.42; 95 % CI 0.21-0.83; P = 0.01) and the residual CIS rate (RR 0.39; 95 % CI 0.19-0.80; P = 0.01). RFS at the 12-month follow-up (RR 1.15; 95 % CI 1.08-1.28; P = 0.0002) and 24-month follow-up (RR 1.26; 95 % CI 1.17-1.35; P < 0.00001) in the FL group was significantly higher than that in the WL group. However, no statistically significant differences were found in PFS at the 12-month follow-up (RR 1.01; 95 % CI 0.99-1.03; P = 0.17) or 24-month follow-up (RR 1.00; 95 % CI 0.97-1.03; P = 0.95). CONCLUSION: FL cystoscopy was related to a reduced residual tumor rate compared with WL cystoscopy in NMIBC, which was also consistent with the Ta, T1 and residual CIS rates. RFS was higher in patients with FL cystoscopy at the 12- to 24-month follow-up.

The utilization status of neoadjuvant chemotherapy in muscle-invasive bladder cancer: a systematic review and meta-analysis.

INTRODUCTION: To give a comprehensive depiction of the utilization status of neoadjuvant chemotherapy (NAC) in muscle invasive bladder cancer (MIBC) worldwide. EVIDENCE ACQUISITION: Potential relevant research papers of Pubmed, Embase, Web of Science, and the Cochrane Library were reviewed to identify eligible studies. Primary outcomes of this meta-analysis were utilization rate of NAC and its utility distribution in different genders, races, ages, countries and temporal trends. The utilization rates of NAC were calculated as 'Proportion (s)' with 95% confidence intervals (CIs) and pooled estimates were calculated by using a random-effect model. EVIDENCE SYNTHESIS: A total of thirteen studies and 35,738 patients were included. The total proportion of NAC applied in MIBC populations prior to radical cystectomy (RC) was 17.2% (95% CI: 12.5-21.9%, I2=99.7%). The comparative analyses showed there were no significant differences existing in different genders or races on NAC utilization rates. In terms of age distribution, <60 age group conferred higher utilization rate of NAC than the older (OR=1.919, 95% CI: 1.671-2.202, P=0.0001). As for regional distribution, our meta-analysis showed that Japan (Proportion: 44.0%, 95% CI: 6.5-81.5%, I2=99.6%) and Sweden (37.9%, 95% CI: 34.9-40.8%) were the top two leading countries which contributed to the most frequent application of NAC. In respect of pathologic responses after NAC, complete, partial and down-staged pathologic responses were achieved in 16.6% (95% CI: 7.4-25.9%, I2=89.7%), 14.6% (95% CI: 0.8-28.5%, I2=89.7%) and 45.0% (95% CI: 17.8-72.2%, I2=98.8%) patients, respectively. CONCLUSIONS: The present study shows the low utilization rate of NAC in MIBC patients. Standardization of the treatment modality of MIBC and promotion of guidelines might be necessary to expedite the adoption of NAC in near future.

The clinicopathological significance and prognostic value of programmed death-ligand 1 in prostate cancer: a meta-analysis of 3133 patients.

BACKGROUND: Programmed death-ligand 1 (PD-L1) is considered an adverse factor predicting poor prognosis in various cancers, but the significance of PD-L1 expression for the prognosis of prostate cancer (PCa) is still unclear. We aimed to investigate the clinicopathological significance and prognostic value of PD-L1 expression in PCa. METHODS: Studies were retrieved from PubMed, Web of Science, Cochrane Library and Embase before March 23, 2020. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were obtained to assess the results. Begg's test was applied to evaluate publication bias. RESULTS: Fourteen studies involving 3133 cases were analyzed. The pooled data showed that both PD-L1 protein expression and PD-L1 DNA methylation (mPD-L1) were negatively associated with biochemical recurrence-free survival, with HRs of 1.67 (95% CI = 1.38-2.06, p < 0.001) and 2.23 (95% CI = 1.51-3.29, p < 0.001), respectively. In addition, PD-L1 overexpression was significantly related to advanced tumor stage (OR = 1.40, 95% CI= 1.13-1.75, p = 0.003), positive surgical margin (OR = 1.36, 95% CI = 1.03-1.78, p = 0.028), higher Gleason score (OR = 1.81, 95% CI = 1.35-2.42, p < 0.001) and androgen receptor positivity (OR = 2.20, 95% CI = 1.61-3.01, p < 0.001), while no significant correlation with age (p = 0.122), preoperative PSA (p = 0.796) or nodal status (p = 0.113) was observed. CONCLUSIONS: The study revealed that high expression of PD-L1 was related to unfavorable prognosis and advanced clinicopathological factors in PCa patients.

Carbohydrates, Glycemic Index, and Glycemic Load in Relation to Bladder Cancer Risk.

Objective: Epidemiologic studies investigating the association between dietary carbohydrates as well as glycemic index and glycemic load (markers of carbohydrate quality) and bladder cancer risk have yielded inconsistent results. The aim of the present meta-analysis is to summarize the evidence on this association. Materials and Methods: A comprehensive literature search of articles published by December 2019 was performed in PubMed, Scopus, and Web of Science databases. A random-effects model was used to calculate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Results: Twelve observational studies were included in the final analysis. There was no evidence of an association between consumption of carbohydrates and bladder cancer risk (pooled OR, 1.04; 95% CI, 0.92-1.17). No statistically significant association between glycemic load and bladder cancer was likewise found (pooled OR, 1.10; 95% CI, 0.85-1.42). However, there was a significant positive association between glycemic index and bladder cancer risk (pooled OR, 1.25; 95% CI, 1.11-1.41). In the dose-response analysis, the pooled OR (95% CI) per 10 units of glycemic index per day was 1.02 (95% CI, 1.01-1.04). Conclusion: In this meta-analysis, glycemic index showed a positive linear association with bladder cancer risk.

The prognostic value of lncRNA SNHG6 in cancer patients.

BACKGROUND: Although tremendous improvement has been seen in cancer diagnosis and treatment, its morbidity and mortality is still high due to lack of ideal biomarkers. An increasing number of studies have demonstrated that the expression of lncRNA small nucleolar RNA host gene 6 (SNHG6) has significantly negative correlation with various cancer prognosis. The present meta-analysis was aimed to clarify the potential of clinical application of SNHG6 in cancers. METHODS: A detailed literature review was conducted by searching through PubMed and Web of Science databases. The expression level of SNHG6, clinicopathological features and survival outcomes were extracted from eligible studies. Pooled analysis was performed with a DerSimonian-Laird random-effect model. The results were further validated through the Cancer Genome Atlas (TCGA) dataset. RESULTS: Five studies with a total of 487 cases were finally included in this meta-analysis. The results demonstrated that a high expression of SNHG6 was significantly associated with an increased risk of poor overall survival (OS) in cancer patients (HR = 2.06, 95% CI 1.56-2.73). Similar results from the TCGA dataset further confirmed our findings. CONCLUSIONS: Overexpressed SNHG6 was significantly associated with poor prognosis in various cancers. Therefore, SNHG6 may become a novel molecular target for treatment and prognostic evaluation.

Reproductive and hormonal factors and bladder cancer risk: a prospective study and meta-analysis.

Bladder cancer is three to four times more common among men than women. The objectives of this study were to explore the association between reproductive and hormonal factors and risk of bladder cancer among women using data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cohort, and to perform a meta-analysis based on cohort studies. After a median of 11.6 years of follow-up, 237 incident bladder cancer cases were identified in PLCO cohort. Compared with menopause at 50-54 years, earlier menopause (< 45 years) was positively but not significantly associated with bladder cancer risk (HR 1.25, 95% CI 0.91-1.71; p = 0.176). In the meta-analysis, parous women had significantly lower bladder cancer risk than nulliparous women (pooled HR 0.79, 95% CI 0.73-0.86). In addition, menopause at an earlier age was significantly associated with a higher risk of bladder cancer (pooled HR 1.22, 95% CI 1.06-1.40). In conclusion, this study indicated a greater risk in bladder cancer among nulliparous women and among women with early menopause. Further studies are needed to understand the underlying mechanisms.

SP1/AKT/FOXO3 Signaling Is Involved in miR-362-3p-Mediated Inhibition of Cell-Cycle Pathway and EMT Progression in Renal Cell Carcinoma.

Emerging evidence has indicated that dysregulation of miR-362-3p is involved in the initiation and progression of several types of human cancers. However, the molecular mechanism of miR-362-3p in renal cell carcinoma (RCC) is still not completely clear. In this study, we found that miR-362-3p was frequently down-regulated in human RCC tissues. Overexpression of miR-362-3p in RCC cells significantly suppressed the proliferation, cell cycle and motility in vitro and in vivo via regulating AKT/FOXO3 signaling. We further confirmed that SP1 was a direct target of miR-362-3p. Knockdown of SP1 expression by a small interfering RNA (siRNA) phenocopied the effect of miR-362-3p overexpression in RCC cells. In conclusion, the current results provide evidence for the role of miR-362-3p in the pathogenesis of RCC and thus miR-362-3p may serve as an attractive candidate for RCC therapy.

The characteristics of androgen receptor splice variant 7 in the treatment of hormonal sensitive prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Accumulating evidence suggests androgen receptor splice variant 7 (AR-V7) may be associated with the prognosis of castration-resistant prostate cancer (CRPC) received novel hormonal therapy while its characteristic and prognosis value in hormonal sensitive prostate cancer is unclear. METHODS: We aimed to evaluate the prognostic role of AR-V7 by progression free survival (PFS) and overall survival (OS) in hormonal sensitive prostate cancer (HSPC), and the AR-V7-positive-proportion difference in HSPC and CRPC. A search of PubMed, Embase, and the Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma; AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Seventeen trials published due December 2019 were enrolled. RESULTS: AR-V7-positive proportion in CRPC was significantly larger than newly diagnosed prostate cancer (PCa) (odds ratio [OR] 7.06, 95% confidence interval [CI] 2.52-19.83, P < 0.001). Subgroup analyses indicated significantly higher AR-V7-positive proportion in CRPC derived from RNA in situ hybridization (OR 65.23, 95% CI 1.34-3171.43, P = 0.04), exosome RNA (OR 3.88, 95% CI 0.98-15.39, P = 0.05) and tissue RNA (OR 10.89, 95% CI 4.13-28.73, P < 0.001). AR-V7-positive patients had a significantly shorter PFS than those who were AR-V7-negative treated with first-line hormonal therapy (hazard ratio [HR] 3.63, 95% CI 1.85-7.10, P < 0.001) and prostatectomy (HR 2.49, 95% CI 1.33-4.64, P = 0.004). OS (HR 5.59, 95% CI 2.89-10.80, P < 0.001) were better in AR-V7-negative than AR-V7-positive HSPC patients treated with first-line hormonal therapy. The limitations of our meta-analysis were differences in study sample size and design, AR-V7 detection assay, and disease characteristics. CONCLUSION: AR-V7-positive proportion was significantly higher in CRPC than that in newly diagnosed PCa. AR-V7 positive HSPC patients portend worse prognosis of first-line hormonal therapy and prostatectomy. Additional studies are warranted to confirm these findings.