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.

Integration analysis identifies MYBL1 as a novel immunotherapy biomarker affecting the immune microenvironment in clear cell renal cell carcinoma: Evidence based on machine learning and experiments.

Background: Previous studies have identified MYBL1 as a cancer-promoting molecule in numerous types of cancer. Nevertheless, the role of MYBL in renal cancer remains unclear. Methods: Genomic and clinical data of clear cell renal cell carcinoma (ccRCC) was get from the Cancer Genome Atlas (TCGA) database. CCK8, colony formation, and 5-ethynyl-2'-deoxyuridine assay were utilized to evaluate the performance of cell proliferation. Cell apoptosis was detected using the flow cytometric analysis. The protein level of MYBL1 in different tissues was evaluated using immunohistochemistry. A machine learning algorithm was utilized to identify the prognosis signature based on MYBL1-derived molecules. Results: Here, we comprehensively investigated the role of MYBL1 in ccRCC. Here, we noticed a higher level of MYBL1 in ccRCC patients in both RNA and protein levels. Further analysis showed that MYBL1 was correlated with progressive clinical characteristics and worse prognosis performance. Biological enrichment analysis showed that MYBL1 can activate multiple oncogenic pathways in ccRCC. Moreover, we found that MYBL1 can remodel the immune microenvironment of ccRCC and affect the immunotherapy response. In vitro and in vivo assays indicated that MYBL1 was upregulated in ccRCC cells and can promote cellular malignant behaviors of ccRCC. Ultimately, an machine learning algorithm - LASSO logistics regression was utilized to identify a prognosis signature based on the MYBL1-derived molecules, which showed satisfactory prediction ability on patient prognosis in both training and validation cohorts. Conclusions: Our result indicated that MYBL1 is a novel biomarker of ccRCC, which can remodel the tumor microenvironment, affect immunotherapy response and guide precision medicine in ccRCC.

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.

Long Noncoding RNA Small Nucleolar Host Gene: A Potential Therapeutic Target in Urological Cancers.

The incidence of urological cancer has been gradually increasing in the last few decades. However, current diagnostic tools and treatment strategies continue to have limitations. Substantial evidence shows that long noncoding RNAs (lncRNAs) play essential roles in carcinogenesis and the progression, treatment response and prognosis of multiple human cancers, including urological cancers, gastrointestinal tumours, reproductive cancers and respiratory neoplasms. LncRNA small nucleolar RNA host genes (SNHGs), a subgroup of lncRNAs, have been found to be dysregulated in tumour cell biology. In this review, we summarize the impacts of lncRNA SNHGs in urological malignancies and the underlying mechanisms.

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.

Metabolic Syndrome Is Not Associated With Prostate Cancer Recurrence: A Retrospective Analysis of a Chinese Cohort.

Objective: Metabolic syndrome (MetS), a common disease that affects many people around the world, has been hypothesized to be associated with human cancers, including prostate cancer (PCa), but the association has not been consistent. The aim of the current study was to evaluate whether MetS and its components are risk factors for PCa biochemical recurrence (BCR) among a cohort of postoperative patients at our hospital in China. Materials and Methods: This retrospective study included 214 patients with PCa who received radical prostatectomy. Differences between groups were estimated using the χ2 test or Student's t-test. BCR rates were calculated according to the Kaplan-Meier method with the log-rank test. A Cox regression analysis was conducted for the multivariate analyses to identify significant predictors of BCR. Results: Of the 214 eligible men, 55 experienced BCR and 24 met the MetS diagnostic criteria. Multivariate Cox model analysis showed that patients with BCR had a higher Gleason score [hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.33-4.76] and positive nerve invasion (HR 3.57, 95% CI 1.85-6.88). MetS was not associated with BCR (HR 0.38, 95% CI 0.13-1.10). Conclusion: BCR is not associated with MetS but is associated with a higher Gleason score and positive nerve invasion.

The Prognostic Value of Androgen Receptor Splice Variant 7 in Castration-Resistant Prostate Cancer Treated With Novel Hormonal Therapy or Chemotherapy: A Systematic Review and Meta-analysis.

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.

Dietary inflammatory index and the risk of prostate cancer: a dose-response meta-analysis.

Emerging epidemiological studies have assessed the potential relationship between the inflammatory potential of diet measured using the dietary inflammatory index (DII) and the risk of prostate cancer and found inconsistent results. The aim of this study was to systematically evaluate this issue using a meta-analysis approach. A comprehensive literature search of papers published through March 2019 was performed in the PubMed and EMBASE databases. The summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a DerSimonian and Laird random effects model. A categorized analysis and linear and nonlinear dose-response analyses were performed. Ten studies met the inclusion criteria for our meta-analysis. The highest DII score category was associated with a significantly higher risk of prostate cancer than the lowest DII score category (OR = 1.73, 95% CI 1.34-2.23). In the dose-response analysis, the summary OR of prostate cancer for an increment of one unit of the DII was 1.10 (95% CI 1.04-1.17). The sensitivity analysis indicated that exclusion of any single study did not materially alter the pooled risk estimates. Finally, there was no evidence of significant publication bias with Begg's test or with Egger's test. In conclusion, this meta-analysis suggests that an increased DII is related to a higher risk of prostate cancer and that the risk increases by 10.0% per unit of the DII. However, further well-designed prospective trials with larger sample sizes should be performed to validate our preliminary findings.

Kaempferol protects ethanol-induced gastric ulcers in mice via pro-inflammatory cytokines and NO.

Gastric ulcers (GUs) are common pathologies that affect many people around the world. Excessive alcohol consumption is one of the main causes of GUs; however, there are still lack of effective drugs for the prevention or therapy of GUs. In this study, we evaluated the protective effects and possible mechanisms of kaempferol (KAE) against acute ethanol-induced lesions to the gastric mucosa in mice. Fasted mice were orally given vehicle (0.9% saline), omeprazole (20 mg/kg), or KAE (40, 80, or 160 mg/kg) for 1 h in different experimental sets prior to the establishment of the GU model by challenge with absolute ethanol (10 ml/kg). Animals were euthanized 1 h after ethanol intake, and their plasma and stomach tissues were subject to further examination. Macroscopic and microscopic lesions, and immunological and biochemical parameters were observed. The effects of inflammation were investigated using the following indicators: tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, myeloperoxidase (MPO), and nitric oxide (NO). Results showed that KAE significantly decreased the ulcer index, increased the preventive index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. KAE decreased MPO activity and pro-inflammatory cytokine (TNF-α, and IL-1ß) levels, and improved NO levels. The gastroprotective activity of KAE might be attributed to the preservation of gastric mucous glycoproteins levels, thus by inhibiting neutrophil accumulation and MPO activity, adjusting the levels of pro-inflammatory cytokines, and improving NO production.