RESUMO
Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Ferroptosis plays a vital role in ccRCC development and progression. We did an update of ferroptosis-related multigene expression signature for individualized prognosis prediction in patients with ccRCC. Differentially expressed ferroptosis-related genes in ccRCC and normal samples were screened using The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses and machine learning methods were employed to identify optimal prognosis-related genes. CARS1, CD44, FANCD2, HMGCR, NCOA4, SLC7A11, and ACACA were selected to establish a prognostic risk score model. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these genes were mainly enriched in immune-related pathways; single-sample Gene Set Enrichment Analysis revealed several immune cells potentially related to ferroptosis. Kaplan-Meier survival analysis demonstrated that patients with high-risk scores had significantly poor overall survival (log-rank P = 7.815 × 10-11). The ferroptosis signature was identified as an independent prognostic factor. Finally, a prognostic nomogram, including the ferroptosis signature, age, histological grade, and stage status, was constructed. Analysis of The Cancer Genome Atlas-based calibration plots, C-index, and decision curve indicated the excellent predictive performance of the nomogram. The ferroptosis-related seven-gene risk score model is useful as a prognostic biomarker and suggests therapeutic targets for ccRCC. The prognostic nomogram may assist in individualized survival prediction and improve treatment strategies.
RESUMO
We conducted a systematic review and meta-analysis of published randomised controlled trials of dapoxetine for premature ejaculation. We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov and Clinical Trials.gov for studies reporting dapoxetine in men with premature ejaculation. Efficacy endpoints included intravaginal ejaculatory latency times (IELT), personal distress related to ejaculation (PDRE) and treatment-emergent adverse events (TEAEs) was used to evaluate safety. Data were analysed using a random-effects model. Electronic search identified 276 papers. The final analysis included eight papers (n = 8422 subjects). Analysis of the pooled results indicated efficacy in both IELT (weighted mean difference (WMD) = 1.67, 95% confidence interval (CI) 1.45-1.89) and PDRE (relative risk = 1.26, 95% CI 1.18-1.35). Subgroup analysis indicated efficacy (i.e. increase in IELT) for 30- and 60-mg on-demand dapoxetine (WMD 1.38 (95% CI 1.01-1.75) and 1.62 (95% CI 1.40-1.84) respectively), as well as daily use of 60 mg dapoxetine (WMD 2.18, 95% CI 1.71-2.64). The safety profile was acceptable. Based on the different effects of magnitude of the three dosing regimens, we recommend a stepwise approach, starting with 30 mg on demand, then 60 mg on demand and finally 60 mg dapoxetine daily.
