Mary Babb Randolph Cancer Center, West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA.
National Institute of Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA.
Int J Mol Sci. 2021 Jul 17;22(14):7658. doi: 10.3390/ijms22147658.
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.
本研究开发了一种新的方法学，将肺鳞状细胞癌（LUSC）队列中的全基因组 microRNA（miRNA）表达谱与 Surveillance，Epidemiology，and End Results（SEER）-Medicare LUSC 患者（n=33897）相关联，作为 T、N 和 M 癌症分期和肿瘤分级的复合肿瘤进展指标的函数。选择的预后和化疗预测 miRNA 与从美国医院收集的非小细胞肺癌（NSCLC）患者样本的 miRNA 表达谱（n=156）以及包括 NCI-60、癌症基因组图谱（TCGA；n=1016）和癌症细胞系百科全书（CCLE；n=117）在内的公共联合体进行了广泛验证。在所有研究的数据集，hsa-miR-142-3p 与良好的预后和化疗敏感性相关。hsa-miRNA-142-3p 靶基因（、、、、、、、和）在 CRISPR-Cas9（n=78）和 RNA 干扰（RNAi）筛选（n=92）的 100%测试 NSCLC 细胞系中对增殖有显著影响。在 NSCLC 短期幸存者中阐明了 hsa-miR-142-3p 介导的途径和功能网络。总体而言，将 SEER-Medicare 数据与综合外部验证相结合的方法可以识别出在肿瘤进展中具有一致表达模式的 miRNA，这对大型 NSCLC 患者群体的预后和化疗反应预测具有潜在意义。
