Low miR-145 and high miR-367 are associated with unfavourable prognosis in resected nonsmall cell lung cancer

Abstract

ABSTRACT: The transcription factors SRY-related HMG box (SOX)2 and octamer-binding transcription factor (OCT)4 regulate the expression of the miR-302–367 cluster. miR-145 regulates SOX2 and OCT4 translation and p53 regulates miR-145 expression. We analysed the expression of the miR-302–367 cluster and miR-145 and the mutational status of p53 in resected nonsmall cell lung cancer (NSCLC) patients and correlated results with time to relapse (TTR). Tumour and paired normal tissue samples were obtained from 70 NSCLC patients. MicroRNA expression was assessed with TaqMan MicroRNA Assays. p53 exons 5 to 8 were sequenced. miR-145 was downregulated (p,0.0001) and miR-367 was upregulated (p,0.0001) in tumour compared with normal tissue. Mean TTR was 18.4 months forpatients with low miR-145 levels and 28.2 months for those with high levels (p50.015). Mean TTR was 29.1 months for patients with low miR-367 levels and 23.4 months for those with high levels (p50.048). TTR was shorter for patients with both unfavourable variables (p50.009). Low miR-145 expression (p50.049), the combination of unfavourable microRNA levels (p50.02) and the combination of low miR-145 with p53 mutations (p50.011) were independent markers of shorter TTR. In conclusion, miR-145 and miR-367 expression could be novel markers for relapse in surgically treated NSCLC. p53 may play a role in modulating miR-145 expression in NSCLC.