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

• Main Authors: Qing Ye, Joseph Putila, Rebecca Raese, Chunlin Dong, Yong Qian, Afshin Dowlati, Nancy Lan Guo
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: International Journal of Molecular Sciences
• Subjects: microRNA (miRNA); prognosis; chemoresponse; non-small-cell lung cancer (NSCLC); CRISPR-Cas9; RNA interference (RNAi)
• Online Access: https://www.mdpi.com/1422-0067/22/14/7658

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