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This study developed a novel methodology to correlate genome-scale microRNA (miRNA) expression profiles in a lung squamous cell carcinoma (LUSC) cohort ( n = 57) with Surveillance, Epidemiology, and End Results (SEER)-Medicare LUSC patients ( n = 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 ( n = 156) and public consortia including NCI-60, The Cancer Genome Atlas (TCGA; n = 1016), and Cancer Cell Line Encyclopedia (CCLE; n = 117). Hsa-miR-142-3p was associated with good prognosis and chemosensitivity in all the studied datasets. Hsa-miRNA-142-3p target genes ( NUP205 , RAN , CSE1L , SNRPD1 , RPS11 , SF3B1 , COPA , ARCN1 , and SNRNP200 ) had a significant impact on proliferation in 100% of the tested NSCLC cell lines in CRISPR-Cas9 ( n = 78) and RNA interference (RNAi) screening ( n = 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.

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