Identification of 5 microRNA biomarkers associated with the prognosis of uveal melanoma

Abstract

To uncover the role of microRNAs in the occurrence and development of uveal melanoma (UM), we used R language packages in this study to analyze the correlations between the expression of microRNA isoforms, their target genes, and the clinical data for UM patients retrieved from The Cancer Genome Atlas (TCGA). We used Weighted Correlation Network Analysis (WGCNA) to divide the expression profiles of different microRNAs into 10 modules, among which blue and yellow modules were associated with UM survival. Hsa-miR-513a-5p, miR-506-3p, miR-508-3p, miR-140-3p, and miR-103a-2-5p were further identified as the top 5 node microRNAs based on the risk scores in both modules using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. After combining these 5 microRNAs into an integrated risk signature, the prognostic performance of the risk signature was evaluated by area under the receiver operating characteristic (AUROC) curve, and their association with UM clinical characteristics was further analyzed using multiple Cox regression. Our results showed that this risk signature was sensitivity and specificity, and could serve as an independent prognostic factor. In addition, Spearman correlation analysis showed that expression of almost all target mRNAs were significantly positively or negatively correlated with the associated microRNAs. The gene ontology (GO), pathways, and disease enrichment analyses also showed that these 5 microRNAs were closely related to the incidence and progression of tumor, indicating their potential for predicting the outcome of UM. Abbreviations: AUROC = receiver operating characteristic, FPKM = fragments per kilobase of exon model per million reads mapped, GO = curve gene ontology, HR = Hazard ratio, KEGG = Kyoto Encyclopedia of Genes and Genomes, LASSO = least absolute shrinkage and selection operator, MCC = Matthews correlation coefficient, OS = overall survival, TCGA = The Cancer Genome Atlas, UM = Uveal melanoma, WGCNA = Weighted Correlation Network Analysis.

Genetics and RNA Regulation of Uveal Melanoma

“…PTEN [254] miR-372 NA SRC3/NCOA3 [217] miR-378* hsa-miR-378a-5p Downregulated in tumors with chromosome 3 monosomy [221] miR-378d hsa-miR-378d Downregulated in high-risk tumors [202] Upregulated in tumor tissues [228] miR-378g hsa-miR-378g Upregulated in tumor tissues [228] miR-429 hsa-miR-429 Regulation of cell proliferation in vitro SRC3/NCOA3 [217] miR-452 hsa-miR-452-5p Associated with high risk [238] miR-4709 NA Associated with high risk [238] miR-506 hsa-miR-506-3p Downregulated in tumors with chromosome 3 monosomy; upregulated in tumors with chromosome 3 monosomy and metastatic disease [221] Downregulated in metastatic tumors [220] miR-506-3p Downregulated in metastatic tumors [240] High levels associated with better survival outcomes [216] miR-507 hsa-miR-507 Downregulated in tumors with chromosome 3 monosomy [221] Low expression associated with poor prognosis [235] miR-508 hsa-miR-508-3p Downregulated in advanced tumors [222] miR-508-3p Downregulated in tumors with chromosome 3 monosomy; upregulated in tumors with chromosome 3 monosomy and metastatic disease [221] miR-508-3p Downregulated in high-vs. low-grade tumors and deceased vs. alive patients; associated with poor prognosis and worse overall survival [239] Downregulated in metastatic tumors [240] High levels associated with better survival outcomes [216] miR-508-5p hsa-miR-508-5p Downregulated in metastatic tumors [240] miR-509-3-5p hsa-miR-509-3-5p Downregulated in tumors with chromosome 3 monosomy; upregulated in tumors with chromosome 3 monosomy and metastatic disease [221] Downregulated in high-vs. low-grade tumors and deceased vs. alive patients; associated with poor prognosis and worse overall survival [239] Downregulated in metastatic tumors [240] miR-509-3p hsa-miR-509-3p Downregulated in tumors with chromosome 3 monosomy; upregulated in tumors with chromosome 3 monosomy and metastatic disease [221] Downregulated in metastatic tumors [240] Downregulated in metastatic tumors [240] miR-513a-5p hsa-miR-513a-5p High levels associated with better survival outcomes...…”

“…In the last year, this topic has been investigated. Sun et al re-analyzed TCGA expression data and identified a signature including five miRNAs (miR-513a-5p, miR-506-3p, miR-508-3p, miR-140-3p, miR-103a-2-5p) representing an independent prognostic factor able to predict the prognosis of UM patients [216]. Another signature comprising three miRNAs (miR-1296, miR-199a, miR-508) was identified by using TCGA expression data and validated in two GEO datasets (GSE84976 [203] and GSE68828 [224]); the authors suggested the prognostic application of this signature in predicting OS [222].…”

Promising and Minimally Invasive Biomarkers: Targeting Melanoma

“…This signature was developed using the five highest-performing serum miRNA expression profiles (hsa-miR-513a-5p, miR-506-3p, miR-508-3p, miR-140-3pand miR-103a-2-5p), which were combined with clinical information and their respective target genes using Weighted Correlation Network Analysis (WGCNA). This risk signature consistently demonstrated the ability to differentiate between low and high-risk groups, as evidenced by Kaplan–Meier analysis ( p < 0.001), ROC curve analysis (accuracy > 0.9) and its status as an independent prognostic factor according to multiple Cox regression analysis (hazard ratio for death of 3.799; 95% CI: 1.903–7.583; p < 0.001) [ 196 ].…”