Prognostic Impact of Melatonin Receptors MT1 and MT2 in Non-Small Cell Lung Cancer (NSCLC)

Abstract

Background: Several studies have investigated the inhibitory effect of melatonin on lung cancer cells. There are no data available on the prognostic impact of melatonin receptors MT1 and MT2 in non-small cell lung cancer (NSCLC). Materials and Methods: Immunohistochemical studies of MT1 and MT2 were conducted on NSCLC (N = 786) and non-malignant lung tissue (NMLT) (N = 120) using tissue microarrays. Molecular studies were performed on frozen fragments of NSCLC (N = 62; real time PCR), NMLT (N = 24) and lung cancer cell lines NCI-H1703, A549 and IMR-90 (real time PCR, western blot). Results: The expression of both receptors was higher in NSCLC than in NMLT. Higher MT1 and MT2 expression levels (at protein and mRNA) were noted in squamous cell carcinomas (SCC) compared to adenocarcinomas (AC). MT1 immunoexpression decreased as both the tumour size and the cancer stage increased in the whole cohort, while MT2 decreased as the cancer stage increased, with lymph node involvement (in the whole study group) and increasing malignancy grade (in SCC). Higher expression of MT2 was associated with a favorable prognosis. MT2 was an independent prognostic factor for overall survival (OS) in all analyzed NSCLC and in smoking patients. Conclusions: Our observations may point to the potential prognostic significance of MT2 in NSCLC.