Purpose: A series of microRNAs (miRNAs) have been identified as associated with the survival of patients with non-small-cell lung cancer (NSCLC). The aim of the present study was to explore whether combination of these experimentally validated individual miRNA biomarkers could be used to further increase their prognostic power in NSCLC.
Patients and methods: Based on previously validated NSCLC prognostic miRNAs, gene signatures that could discriminate high-risk subgroups with poor clinical outcome in four NSCLC miRNA expression datasets (GSE13937, GSE16025, The Cancer Genome Atlas Lung Adenocarcinoma, and TCGA lung squamous cell carcinoma) were developed using the SurvMicro tool. The potential of the miRNA signature established was validated by quantitative real-time PCR analysis of clinical NSCLC samples, and its prognostic power evaluated using the survivalROC method.
Results: We developed two miRNA signatures with prognostic significance for NSCLC, comprising 12- and 7-miRNAs. The 7-miRNA signature (miR-148b, miR-365, miR-32, miR-375, miR-21, miR-125b, and miR-155) was a subset of a 12-miRNA set that retained prognostic power across NSCLC cohorts. Compared with previously established miRNA signatures, our 7-miRNA signature has similar potential, while comprising fewer miRNA components. The prognostic ability of the 7-miRNA signature was validated experimentally in an independent NSCLC cohort using real-time PCR (HR=3.4847, 95% CI=1.3693–8.8680, P =0.0092), and this signature, combined with tumor pathological stage, had superior prognostic ability compared with tumor stage alone.
Conclusion: Our data indicate that the established 7-miRNA signature is simple, robust, and may have greater clinical prognostic utility for patients with NSCLC.
Keywords: lung cancer, gene signature, overall survival, The Cancer Genome Atlas, TCGA, risk classification