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

Jablonska Jablonska,Glatzel-Plucinska Glatzel-Plucinska,Pawelczyk Pawelczyk,Piotrowska Piotrowska,Dziegiel Dziegiel,Nowinska Nowinska,Partynska Partynska,Podhorska-Okolow Podhorska-Okolow,Katnik Katnik

doi:10.3390/cancers11071001

Jablonska Jablonska, Glatzel-Plucinska Glatzel-Plucinska + Show 7 more

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https://doi.org/10.3390/cancers11071001

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Journal: Cancers	Publication Date: Jul 17, 2019
Citations: 17	License type: CC BY 4.0

Affiliation: Wroclaw Medical University

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.

Highlights

Lung cancer is one the most frequently diagnosed types of cancer and the leading cause of cancer-related deaths
The results were considered statistically significant at p < 0.05 in all the analyses. Both MT1 and MT2 receptors are expressed in non-small cell lung cancer (NSCLC) cases, it seems that the MT2 receptor predominates in this type of tumor
The observed elevated expression of melatonin receptors both at the protein and mRNA levels in the squamous cell carcinoma (SCC) subtype suggests their potential role in lung cancer biology

Summary

Introduction

Lung cancer is one the most frequently diagnosed types of cancer and the leading cause of cancer-related deaths. Small cell lung cancer (highly malignant and mostly caused by smoking) accounts for about 15% of all cases [2]. Non-small cell lung cancer (85% of cases) includes three histological types: adenocarcinoma (AC) (40%, most often diagnosed in women and non-smokers), squamous cell carcinoma (SCC) (30%, most commonly found in smoking men) and large cell carcinoma (15%, rapid growth and spread) [2,3]. 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). 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. Higher expression of MT2 was associated with a favorable prognosis

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