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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., In this study, we investigated the survival profiles based on conditional survival estimates in metastatic clear cell renal cell carcinoma (mccRCC) patients treated with cytoreductive surgery of primary tumor. We found that COS and CCSS improved with time dynamically in all mccRCC patients treated with cytoreductive surgery of primary tumor.

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 (m6A) 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 m6A 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., miR‐501‐3p was significantly down‐regulated in human RCC cell lines and tissues. Moreover, WTAP was confirmed as the direct target gene of miR‐501‐3p. RCC progression is regulated via the miR‐501‐3p/WTAP/CDK2 axis and is inhibited by the overexpression of the microRNA.

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.

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.

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.

The current study presents a case of primary prostatic extra-gastrointestinal stromal tumor (EGIST) in a 43-year-old man who suffered acute urinary retention. The serum level of prostate-specific antigen was normal. Imaging examinations demonstrated a diffusely enlarged prostate compressing the rectum without evidence of metastasis. After excluding the possibility of secondary involvement by a rectal GIST, the pathologic diagnosis of primary prostatic EGIST was established based on microscopic study, immunohistochemistry, and molecular analysis. This patient is the first case with primary EGISTs of prostate received imatinib mesylate as neoadjuvant and adjuvant therapy reported in the literature to date. We hope this case could provide the experience of diagnosis and treatment of primary prostatic EGISTs.

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.

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.

Highlights • 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. • We enrolled 24 studies with 2307 eligible patients for a systemic review and meta-analysis. • AR-V7 positivity was associated with higher Gleason score, bone or any site metastasis, presence of pain and worse ECOG performance score in CRPC. • Therefore, AR-V7 positivity may be a particular type of prostate cancer subtype in CRPC., 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

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.

BackgroundTumor-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.MethodsWe 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.ResultsBoth 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.ConclusionsTAMs could be potential biomarkers for prognosis and novel targets for immunotherapy in ccRCC. Further researches are warranted to validate our results.

Genomic imprinting has been found to be involved in human physical development and several diseases. The DLK1-DIO3 imprinted domain is located on human chromosome 14 and contains paternally expressed protein-coding genes (DLK1, RTL1, DIO3) and numerous maternally expressed ncRNA genes (MEG3, MEG8, antisense RTL1, miRNAs, piRNAs, and snoRNAs). Emerging evidence has implicated that dysregulation of the DLK1-DIO3 imprinted domain especially the imprinted ncRNAs is critical for tumor progressions. Multiple miRNAs and lncRNAs have been investigated in urological cancers, of which several are transcribed from this domain. In this review, we present current data about the associated miRNAs, lncRNAs, and piRNAs and the regulation of differentially methylated regions methylation status in the progression of urological cancers and preliminarily propose certain concepts about the potential regulatory networks involved in DLK1-DIO3 imprinted domain.

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.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).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.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).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.

PurposeThis study aimed to evaluate the prognostic role of AR-V7 in terms of prostate-specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) in CRPC patients treated with novel hormonal therapy (NHT) (Abiraterone and Enzalutamide) or taxane-based chemotherapy (Docetaxel and Cabazitaxel).MethodsA comprehensive literature search was conducted on PubMed, Embase, and the Web of Science from inception to February 2020. Studies focusing on the prognostic values of AR-V7 in CRPC patients treated with NHT or chemotherapy were included in our meta-analysis. The OS and PFS were analyzed based on Hazard ratios (HRs) and 95% confidence intervals (CIs). Furthermore, Odds ratios (ORs) and 95% CIs were summarized for the AR-V7 conversion after treatment and the PSA response.ResultsThe AR-V7 positive proportion increased significantly after NHT treatment (OR 2.56, 95% CI 1.51–4.32, PConclusionNHT treatment increased AR-V7 positive proportion whereas chemotherapy decreased it. Moreover, AR-V7 positivity correlated with lower PSA response, poorer PFS, and OS in CRPC treated with NHT, and shorter OS in patients receiving chemotherapy.

BACKGROUND Accumulating studies indicate AR-V7 may be related to the poor prognosis of castration resistance prostate cancer (CRPC), while the evidence of the clinicopathological characteristics of AR-V7 is rare. METHODS To evaluate the clinicopathological features of AR-V7 in CRPC patients. 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. Twenty-four trials published due February 2020 were enrolled. RESULTS The proportion of Gleason score ≥ 8 was significantly higher in AR-V7-positive CRPC (69.5%) than negative (54.9%) (OR 1.68, 95% CI 1.25–2.25, PCONCLUSIONS AR-V7 positivity was associated with higher Gleason score, bone or any site metastasis, presence of pain and worse ECOG performance score in CRPC, but not related to tumor stage or lymph node metastasis. More studies are needed to confirm these findings.

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.

To give a comprehensive depiction of the utilization status of neoadjuvant chemotherapy (NAC) in muscle invasive bladder cancer (MIBC) worldwide.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.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%, IThe 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.

Additional file 1: Figure S1. The funnel plot for meta-analysis of the AR-V7 positive proportion in newly diagnosis prostate cancer and CRPC. Figure S2. The funnel plot for meta-analysis of the progression free survival of first-line hormonal therapy in HSPC of different AR-V7 status. Figure S3. The funnel plot for meta-analysis of the overall survival of first-line hormonal therapy in HSPC of different AR-V7 status. Table S1. Target specimens and AR-V7 detection assay of studies in the positive proportion meta-analysis in newly diagnosed PCa and CRPC. Table S2. Definition of PSA response, PFS and OS in the studies included in the meta-analysis of prognosis for hormonal therapy and chemotherapy in different AR-V7 states.

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.

Small RNAs play an important role in gene regulatory networks. The gene suppressive effect of small RNAs was previously the dominant focus of studies, but during the recent decade, small RNA-induced gene activation has been reported and has become a notable gene manipulation technique. In this study, a putative tumor suppressor, INTS6, was activated by introducing a promoter-targeted small RNA (dsRNA-915) into castration-resistant prostate cancer (CRPC) cells. Unique dynamics associated with the gene upregulation phenomenon was observed. Following gene activation, cell proliferation and motility were suppressed in vitro. Downregulation of Wnt/β-catenin signaling was observed during the activation period, and the impairment of β-catenin degradation reversed the tumor suppressor effects of INTS6. These results suggest the potential application of small activating RNAs in targeted gene therapy for CRPC.