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MicroRNAs (miRNAs) are endogenous non-coding RNAs that negatively regulate the expression of downstream targeted mRNAs. Increasing evidence has suggested that miRNAs act as tumor suppressors or oncogenes to interfere the progression of cancers. Here, we showed that miR-204-3p was decreased in bladder cancer tissues and cell lines. Down-regulation of miR-204-3p was significantly associated with a poor prognosis in bladder cancer patients. Overexpression of miR-204-3p inhibited proliferation and induced apoptosis in bladder cancer cells. Furthermore, miR-204-3p was found to bind to the 3′-untranslated region (UTR) of the lactate dehydrogenase (LDHA), which consequently reduced the expression of both mRNA and protein of LDHA. Interestingly, overexpression of miR-204-3p decreased glucose consumption and lactate production of bladder cancer cells. Overexpression of LDHA relieved the growth inhibition and cell apoptosis enhancement by miR-204-3p in bladder cancer cells. These results demonstrated that miR-204-3p negatively modulated the proliferation of bladder cancer cells via targeting LDHA-mediated glycolysis. MiR-204-3p might be a promising candidate for designing anticancer medication.

One of the major features of prostate cancer (PCa) is its heterogeneity, which often leads to uncertainty in cancer diagnostics and unnecessary biopsies as well as overtreatment of the disease. Novel non-invasive tests using multiple biomarkers that can identify clinically high-risk cancer patients for immediate treatment and monitor patients with low-risk cancer for active surveillance are urgently needed to improve treatment decision and cancer management. In this study, we identified 14 promising biomarkers associated with PCa and tested the performance of these biomarkers on tissue specimens and pre-biopsy urinary sediments. These biomarkers showed differential gene expression in higher- and lower-risk PCa. The 14-Gene Panel urine test (PMP22, GOLM1, LMTK2, EZH2, GSTP1, PCA3, VEGFA, CST3, PTEN, PIP5K1A, CDK1, TMPRSS2, ANXA3, and CCND1) was assessed in two independent prospective and retrospective urine study cohorts and showed high diagnostic accuracy to identify higher-risk PCa patients with the need for treatment and lower-risk patients for surveillance. The AUC was 0.897 (95% CI 0.939–0.855) in the prospective cohort (n = 202), and AUC was 0.899 (95% CI 0.964–0.834) in the retrospective cohort (n = 97). In contrast, serum PSA and Gleason score had much lower accuracy in the same 202 patient cohorts [AUC was 0.821 (95% CI 0.879–0.763) for PSA and 0.860 (95% CI 0.910–0.810) for Gleason score]. In addition, the 14-Gene Panel was more accurate at risk stratification in a subgroup of patients with Gleason scores 6 and 7 in the prospective cohort (n = 132) with AUC of 0.923 (95% CI 0.968–0.878) than PSA [AUC of 0.773 (95% CI 0.852–0.794)] and Gleason score [AUC of 0.776 (95% CI 0.854–0.698)]. Furthermore, the 14-Gene Panel was found to be able to accurately distinguish PCa from benign prostate with AUC of 0.854 (95% CI 0.892–0.816) in a prospective urine study cohort (n = 393), while PSA had lower accuracy with AUC of 0.652 (95% CI 0.706–0.598). Taken together, the 14-Gene Panel urine test represents a promising non-invasive tool for detection of higher-risk PCa to aid treatment decision and lower-risk PCa for active surveillance.

BackgroundProgrammed death 1/ligand 1 (PD-1/L1) inhibitors have acceptable antitumor activity in patients with platinum-resistant urothelial cancer (UC). However, the reliability and comparability of the antitumor activity, safety profiles and survival outcomes of different immune checkpoint inhibitors are unknown. Our objective was to compare the clinical efficacy and safety of anti–PD-1/PD-L1 therapies in platinum-resistant UC patients.MethodsWe reviewed the published trials from the PubMed, Embase and Cochrane Library databases up to August 2020. A well-designed mirror principle strategy to screen and pair trial characteristics was used to justify indirect comparisons. The primary end point was the objective response rate (ORR). The safety profile and survival outcomes were also evaluated. The restricted mean survival time (RMST) up to 12 months was calculated.ResultsEight studies including 1,666 advanced or metastatic UC patients (1,021 patients with anti–PD-L1 treatment and 645 patients with anti–PD-1 treatment) met the study criteria. The ORRs of anti–PD-1 and PD-L1 therapy were 22% (95% CI, 18%–25%) and 15% (95% CI, 13%–17%) with all studies combined. The proportions of the treated population with a confirmed objective response (I2 = 0; P = 0.966; HR, 1.60; 95% CI, 1.23–2.07; P < 0.001) and disease control (I2 = 30.6%; P = 0.229; HR, 1.35; 95% CI, 1.10–1.66; P = 0.004) were higher with anti–PD-1 therapy than with anti–PD-L1 therapy. The treatment-related adverse events (AEs) (I2 = 78.3%; P = 0.003; OR, 1.09; 95% CI, 0.65–1.84; P = 0.741) and grade 3–5 treatment-related AEs (I2 = 68.5%; P = 0.023; OR, 1.69; 95% CI, 0.95–3.01; P = 0.074) of anti–PD-1 therapy were comparable to those of anti–PD-L1 therapy. The RMST values at the 12-month follow-up were 9.4 months (95% CI,: 8.8–10.0) for anti–PD-1 therapy and 9.3 months (95% CI, 8.8–9.7) for anti–PD-L1 therapy (z = 0.26, P = 0.794). There was no significant difference between patients in the anti–PD-1 and anti–PD-L1 groups (12-month overall survival (OS): 43% versus 42%, P = 0.765. I2 = 0; P = 0.999; HR, 0.95; 95% CI, 0.83–1.09; P = 0.474).ConclusionsThe results of our systematic comparison suggest that anti–PD-1 therapy exhibits better antitumor activity than anti–PD-L1 therapy, with comparable safety profiles and survival outcomes. These findings may contribute to enhanced treatment awareness in patients with platinum-resistant UC.

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Purpose: We explored whether the modified American Joint Committee on Cancer tumor-node-metastasis prognostic stage group IV can be individualized in a large population-based cohort of surgically treated invasive upper tract urothelial carcinoma (UTUC) patients. Methods: Invasive UTUC patients from the Surveillance, Epidemiology and End Results database (2004-2015) were screened for inclusion. A total of 10,482 eligible cases were identified. Cancer-specific survival (CSS) after surgery was analyzed using Kaplan-Meier plots. Results: According to the most recent pathological prognostic group classification, the 5-year mortality rates of T4NxM0 (n=493), TxN1M0 (n=597), TxN2M0 (n=424) and pTxNxM1 (n=677) patients were 41.1% (95% CI 35.2% to 47.0%), 38.6% (95% CI 33.1% to 44.1%), 40.4% (95% CI 33.0% to 47.8%) and 14.2% (95% CI 9.9% to 18.5%), respectively (T4N0M0 vs. TxNxM1, P <0.001; TxN1M0 vs. TxNxM1, P <0.001; TxN2M0 vs. TxNxM1, P <0.001). Stage IV tumors were subdivided on the basis of the mortality data (Modification 1): stage IVa tumors were considered nonmetastatic (T4NxM0, TxN1-2M0; 5-year CSS 39.9%), and stage IVb tumors were considered metastatic (pTxNxM1; 5-year CSS 14.2%). Stage IV tumors were also subdivided according to the grade classification (Modification 2): stage IVa tumors were considered low grade (T4NxM0, TxN1-2M0, TxNxM1; G1-2; n=141), and stage IVb tumors were considered metastatic (T4NxM0, TxN1-2M0, TxNxM1; G3-4; n=2050). The 5-year CSS rates for stage IVa and IVb patients were 76.3% (95% CI 68.7% to 83.9%) and 31.4% (95% CI 28.5% to 34.3%), respectively ( P <0.001). Conclusions: Stage IV patients were stratified into two prognostically different risk groups depending on metastasis or grade. The subclassification of stage IV can increase the level of prognostic detail and individualize the prediction of survival in invasive UTUC patients.