| Autor: |
Ye Q; Mary Babb Randolph Cancer Center, West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA., Putila J; Mary Babb Randolph Cancer Center, West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA., Raese R; Mary Babb Randolph Cancer Center, West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA., Dong C; Mary Babb Randolph Cancer Center, West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA., Qian Y; National Institute of Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA., Dowlati A; Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA., Guo NL; Mary Babb Randolph Cancer Center, West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA. |
| Abstrakt: |
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. |
