Objective Evidence shows that gene mutation is a significant proportion of genetic factors associated with prostate cancer. The DNA damage response (DDR) is a signal cascade network that aims to maintain genomic integrity in cells. This comprehensive study was performed to determine the link between different DNA damage response gene mutations and prostate cancer. Materials and methods A systematic literature search was performed using PubMed, Web of Science, and Embase. Papers published up to February 1, 2022 were retrieved. The DDR gene mutations associated with prostate cancer were identified by referring to relevant research and review articles. Data of prostate cancer patients from multiple PCa cohorts were obtained from cBioPortal. The OR or HR and 95% CIs were calculated using both fixed-effects models (FEMs) and random-effects models (REMs). Results Seventy-four studies were included in this research, and the frequency of 13 DDR genes was examined. Through the analysis of 33 articles that focused on the risk estimates of DDR genes between normal people and PCa patients, DDR genes were found to be more common in prostate cancer patients (OR = 3.6293 95% CI [2.4992; 5.2705]). Also, patients in the mutated group had a worse OS and DFS outcome than those in the unmutated group ( P < .05). Of the 13 DDR genes, the frequency of 9 DDR genes in prostate cancer was less than 1%, and despite differences in race, BRCA2 was the potential gene with the highest frequency (REM Frequency = .0400, 95% CI .0324 - .0541). The findings suggest that mutations in genes such as ATR, BLM, and MLH1 in PCa patients may increase the sensitivity of Olaparib, a PARP inhibitor. Conclusion These results demonstrate that mutation in any DDR pathway results in a poor prognosis for PCa patients. Furthermore, mutations in ATR, BLM, and MLH1 or the expression of POLR2L, PMS1, FANCE, and other genes significantly influence Olaparib sensitivity, which may be underlying therapeutic targets in the future.
BackgroundThe association between clear cell renal cell carcinoma (ccRCC) and disulfidoptosis remains to be thoroughly investigated.MethodsWe conducted multiple bioinformatics analyses, including prognostic analysis and cluster analysis, using R software. Additionally, we utilized Quantitative Real-time PCR to measure RNA levels of specific genes. The proliferation of ccRCC was assessed through CCK8 and colony formation assays, while the invasion and migration of ccRCC cells were evaluated using the transwell assay.ResultsIn this study, utilizing data from multiple ccRCC cohorts, we identified molecules that contribute to disulfidoptosis. We conducted a comprehensive investigation into the prognostic and immunological roles of these molecules. Among the disulfidoptosis-related metabolism genes (DMGs), LRPPRC, OXSM, GYS1, and SLC7A11 exhibited significant correlations with ccRCC patient prognosis. Based on our signature, patients in different groups displayed varying levels of immune infiltration and different mutation profiles. Furthermore, we classified patients into two clusters and identified multiple functional pathways that play important roles in the occurrence and development of ccRCC. Given its critical role in disulfidoptosis, we conducted further analysis on SLC7A11. Our results demonstrated that ccRCC cells with high expression of SLC7A11 exhibited a malignant phenotype.ConclusionsThese findings enhanced our understanding of the underlying function of DMGs in ccRCC.
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