Peer Review #2 of "Identification of a five-miRNA signature predicting survival in cutaneous melanoma cancer patients (v0.1)"

Abstract

Background. Cutaneous melanoma (CM) is the deadliest form of skin cancer. Numerous studies have revealed that microRNAs (miRNAs) are expressed abnormally in melanoma tissues. Our work aimed to assess multiple miRNAs using bioinformatic analysis in order to predict the prognoses of cutaneous melanoma patients. Methods. The microarray dataset GSE35579 was downloaded from the Gene Expression Omnibus (GEO) database to detect the differential expression of miRNAs (DEMs), including 41 melanoma (primary and metastatic) tissues and 11 benign nevi. Clinical information and miRNA sequencing data of cutaneous melanoma tissues were downloaded from the Cancer Genome Atlas database (TCGA) to assess the prognostic values of DEMs. Additionally, the target genes of DEMs were anticipated using miRanda, miRmap, TargetScan, and PicTar. Finally, functional analysis was performed using selected target genes on the Annotation, Visualization and Integrated Discovery (DAVID) website. Results. After performing bioinformatic analysis, a total of 185 DEMs were identified: 80 upregulated miRNAs and 105 downregulated miRNAs. A five-miRNA (miR-25, miR-204, miR-211, miR-510, miR-513c) signature was discovered to be a potential significant prognostic biomarker of cutaneous melanoma when using the Kaplan-Meier survival method (P = 0.001). Univariate and multivariate Cox regression analyses showed that the five-miRNA signature could be an independent prognostic marker (HR = 0.605, P = 0.006) in cutaneous melanoma patients. Biological pathway analysis indicated that the target genes may be involved in PI3K-Akt pathways, ubiquitin-mediated proteolysis, and focal adhesion. Conclusion. The identified five-miRNA signature may serve as a prognostic biomarker, or as a potential therapeutic target, in cutaneous melanoma patients .