摘要
Background:Prostate adenocarcinoma(PRAD)is one of the most commonly diagnosed cancers in men.Expanding evidence suggests a significant association between cancer progression and RNA modifications.However,our knowledge of the link between m^(5)C and hm^(5)C pathways with PRAD is limited.Therefore,we aimed to explore the diagnostic and prognostic values of m^(5)C and hm^(5)C regulators in PRAD.Methods:In this study,genetic alterations in m^(5)C and hm^(5)C regulators were identified using publicly available databases.Expression levels of regulators in PRAD samples were retrieved via the RTCGA package in the R environment.Differentially expressed genes in these pathways between tumor and non-tumor samples were identified using the R‘limma’package.Correlation among m^(5)C and hm^(5)C pathway members was examined employing the‘Hmisc’package in R.We utilized the‘survminer’package in R for applying the Kaplan-Meier method to estimate the overall survival rate of m^(5)C and hm^(5)C regulators.The discrimination power of selected regulators between tumor and non-tumor samples was analyzed by the receiver operating characteristic curve.Furthermore,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were carried out to enrich the affected biological processes and pathways.Results:Differentially expressed genes in these pathways between tumor and non-tumor samples,correlation among m^(5)C and hm^(5)C pathway members,and prognostic value of the regulators were evaluated.Obtained results unveiled the mRNA level differences as the key genetic alterations for m^(5)C and hm^(5)C regulators between tumor and non-tumor samples.UHRF1,TET3,and NEIL1 were significantly upregulated in tumor samples,whereas MECP2 and EGR1 were significantly downregulated for m^(5)C and hm^(5)C regulators.UHRF1,DNMT1,NSUN2,NSUN4,C1orf77,C3orf37,WDR77,NEIL1,and TDG genes were identified as candidate prognostic markers of overall survival.The upregulated genes in patient samples with genetic alterations in m^(5)C and hm^(5)C pathways enriched cell cycle-related processes.Conclusion:In summary,our findings suggest that the m^(5)C and hm^(5)C regulators might play a role in PRAD development by activation of proliferation,and the UHRF1,NSUN2,and NEIL1 genes have the potential to be utilized as clinical biomarkers.Established correlative relationships require experimental validation through functional studies in prostate cancer cell lines.
基金
Health Institutes of Turkey(TUSEB
Project No.TA01-4213)for the financial support of the present study.
