Abstract 4149: Pathway-based serum microRNA profiling and late-stage non-small cell lung cancer survival

Abstract

Abstract Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer mortality in the world. Nearly half of NSCLC patients are diagnosed with late-stage (stage III or stage IV) disease with an overall 5-year survival rate of less than 15%. Deregulation of microRNAs (miRNAs) is involved in cancer development, progression, and prognosis. Circulating miRNAs have been suggested as promising biomarkers for early detection, diagnosis, and prognosis of cancer. This ongoing study is to utilize a pathway-based approach to screen and validate serum miRNA profiles as predictors of survival using a large patient cohort of 348 late-stage NSCLC patients. In the testing set, pre-treatment serum miRNA profiles of four good- (survival time > 24 months) and four poor-survival (survival time < 6 months) patients were compared by Taqman miRNA microarray. 145 highly expressed serum miRNAs were identified from initial screening and 37 of them were mapped onto the 3′UTRs of a panel of 23 genes in TGF-β signaling pathway using computer-assisted miRNA target prediction program. All 37 miRNA candidates were subject to large-scale single-probe quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The expression level of serum miR-30d, which targets TGFBR2 and was a previously reported serum marker for early-stage lung cancer survival, was significantly higher in the poor-survival group than the good-survival group (P = 0.0208) in our study population of late-stage lung cancer. The level of serum miR-93-3p that targets SMAD7 was significantly higher in the poor-survival group than the good-survival group (P = 9x10−6). The 2-year overall survival rate in patients with high serum miR-93-3p expression was significantly lower than that in those with low expression with an adjusted HR of 1.59 (95% CI, 1.24 - 2.03) (P = 2x10−4). In contrast, serum level of let-7g, that targets SMAD2, TGFBR1 and the activin A receptor family was significantly lower in the poor-survival group than in the good-survival group (P = 7x10−4), and patients with high serum let-7g expression was associated with a significantly better two-year survival (HR=0.48, 95% CI, 0.37 - 0.62, P = 1x10−8). Our results suggest that serum miR-30d, miR-93-3p and let-7g may become valuable biomarkers for survival in late-stage NSCLC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4149. doi:1538-7445.AM2012-4149