Identification of Prognostic and Chemopredictive MicroRNAs for Non-Small-Cell Lung Cancer by Integrating SEER-Medicare Data

This study developed a novel methodology to correlate genome-scale microRNA (miRNA) expression profiles in a lung squamous cell carcinoma (LUSC) cohort ( = 57) with Surveillance, Epidemiology, and End Results (SEER)-Medicare LUSC patients ( = 33,897) as a function of composite tumor progression indicators of T, N, and M cancer stage and tumor grade. The selected prognostic and chemopredictive miRNAs were extensively validated with miRNA expression profiles of non-small-cell lung cancer (NSCLC) patient samples collected from US hospitals ( = 156) and public consortia including NCI-60, The Cancer Genome Atlas (TCGA; = 1016), and Cancer Cell Line Encyclopedia (CCLE; = 117). Hsa-miR-142-3p was associated with good prognosis and chemosensitivity in all the studied datasets. Hsa-miRNA-142-3p target genes (, , , , , , , , and ) had a significant impact on proliferation in 100% of the tested NSCLC cell lines in CRISPR-Cas9 ( = 78) and RNA interference (RNAi) screening ( = 92). Hsa-miR-142-3p-mediated pathways and functional networks in NSCLC short-term survivors were elucidated. Overall, the approach integrating SEER-Medicare data with comprehensive external validation can identify miRNAs with consistent expression patterns in tumor progression, with potential implications for prognosis and prediction of chemoresponse in large NSCLC patient populations.