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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]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]