mIR-99a-5p and mIR-148a-3p as Candidate Molecular Biomarkers for the Survival of Lung Cancer Patients

Abstract

MicroRNA (miRNA) has emerged as a promising biomarker for improving the current state of an early lung cancer diagnosis. Multiple studies have reported that circulating miRNAs are usually combined in a single panel in determining the risk of lung cancer. In this study, we sought to identify the potential miRNAs as biomarkers for the survival of lung cancer patients. The microarray analysis was performed on the isolated miRNA samples of formalin-fixed lung cancer tissues from Malaysian populations. The correlation between miRNA expression and lung adenocarcinoma (LUAD) patient survival was predicted using TGGA data, followed by extensive in silico analyses, including miRNA target gene identification, protein-protein interaction (PPI) network construction, subnetwork (SN) detection, functional enrichment analysis, gene-disease associations, and survival analysis in advanced-stage LUAD. Overall, two promising miR-99a-5pand miR-148a-3p were upregulated in the patients with good survival. We found that 64 miR-99a-5p and 95 miR-148a-3ptarget genes were associated with poor prognosis and highly participated in cancer-associated processes, such as apoptosis, mRNA transport and cell-cell adhesion. The density score of 4.667, 3.333, and 3.000 in respective SN1, SN2, and SN3 showed the significant subnetworks of constructed PPI leading to the identification of 17 targets, of which ~79% of them involved in neoplastic diseases. Four high-confidence target genes (SUDS3, TOMM22, KPNA4, and HMGB1) were associated with worse overall survival in LUAD patients, implying their critical roles in LUAD pathogenesis. These findings shed additional light on the roles of miR-99a-5p and miR-148a-3p as potential biomarkers for LUAD survival.