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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 3ʹ 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: This 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). Methods: A 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. Results: The AR-V7 positive proportion increased significantly after NHT treatment (OR 2.56, 95% CI 1.51–4.32, P<0.001), however, it declined after chemotherapy (OR 0.51, 95% CI 0.28–0.93, P=0.003). AR-V7-positive patients showed a significantly decreased PSA response rate after NHT (OR 0.13, 95% CI 0.09–0.19, P<0.001) but not statistically significant for chemotherapy (OR 0.63, 95% CI 0.40-1.01, P=0.06). Notably, PFS (HR 3.56, 95% CI 2.53–5.01, P<0.001) and OS (HR 4.47, 95% CI 3.03–6.59, P<0.001) were worse in AR-V7-positive ttreated with NHT. Similarly, AR-V7 positivity correlated with poor prognosis after chemotherapy as evidenced by shorter OS (HR 1.98, 95% CI 1.48-2.66, P<0.001) and a significantly shorter PFS (HR 1.35, 95% CI 0.97-1.87, P=0.07). Conclusion: NHT 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (Copyright © 2021. Published by Elsevier Inc.)

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&#95;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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Chen, Ying, Ma, Shen, Li, Wang, Lin, Liu, Zheng and Xie.)

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%, I 2 =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%, I 2 =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%, I 2 =89.7%), 14.6% (95% CI: 0.8-28.5%, I 2 =89.7%) and 45.0% (95% CI: 17.8-72.2%, I 2 =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.

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.

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., (Copyright © 2020 Zhu, Wang, Shen, Zheng and Xu.)