Integrative Analysis of MicroRNA and Gene Interactions Associated with BRAF Gene Mutation in Melanoma

Backgrounds: Melanoma is the deadliest skin malignancy, and its incidence rates have tripled inthe last ۳۰ years. Due to the prevalence of V۶۰۰E mutation in the BRAF gene in melanomacases, integrative analysis of expression profiles of both mRNA and miRNA in the same sampleassociated with BRAF mutation could improve diagnosis and prognosis. In this study, we useWeighted Gene Co-expression Network Analysis (WGCNA) as a systems biology method tounderstand correlations among genes and group genes into modules that typically havecoordinated biological functions and regulatory mechanisms and investigate the hub genesrelated to miRNA–gene interactions in melanoma prognosis.Materials and Methods: We downloaded clinical, mRNA, and miRNA microarray data fromTCGA and BRAF mutation status data from cBioportal using R software. We divided the tumorsamples into two molecular trait groups: mutated and non-mutated BRAF. Integrative analysis ofmelanoma transcriptomic data was conducted using WGCNA.Results: To reach the scale-free topology, we clustered samples with a threshold power of ۵. ۱۱module eigengenes were identified. Modules of highly correlated genes and miRNAs in mutatedand non-mutated BRAF groups were detected separately using a heatmap. The purple modulegenes had a ۰.۱۷ correlation with the p-value = ۳e-۰۴ in the non-mutated BRAF group, and theblack module genes had a ۰.۲۵ correlation with the p-value = ۳e-۰۵ in the mutated BRAF group.Conclusion: We showed that BRAF mutation had an enormous impact on gene expression at themRNA and miRNA levels.

کلیدواژه ها:

Melanoma ، BRAF ، WGCNA ، Integrative analysis ، Gene expression