Identification by MicroRNA Analysis of Environmental Risk Factors Bearing Pathogenic Relevance in Non-Smoker Lung Cancer.

Alberto Izzotti,Antonella Agodi,Margherita Ferrante,Salvatore Sciacca,Gabriela Coronel Vargas,Martina Barchitta,Simona Coco,Andrea Maugeri,Gea Oliveri Conti,Giuseppina Blanco,Alessandra Pulliero,Cristina Colarossi

doi:10.3390/jpm11070666

Abstract

MicroRNA and DNA adduct biomarkers may be used to identify the contribution of environmental pollution to some types of cancers. The aim of this study was to use integrated DNA adducts and microRNAs analyses to study retrospectively the contribution of exposures to environmental carcinogens to lung cancer in 64 non-smokers living in Sicily and Catania city near to the Etna volcano. MicroRNAs were extracted from cancer lung biopsies, and from the surrounding lung normal tissue. The expression of 2549 human microRNAs was analyzed by microarray. Benzo(a)Pyrene-DNA adducts levels were analyzed in the patients’ blood by HPLC−fluorescence detection. Correlations between tetrols and environmental exposures were calculated using Pearson coefficients and regression variable plots. Compared with the healthy tissue, 273 microRNAs were downregulated in lung cancer. Tetrols levels were inversely related both with the distance from Etna and years since smoking cessation, but they were not significantly correlated to environmental exposures. The analysis of the microRNA environmental signatures indicates the contribution of environmental factors to the analyzed lung cancers in the following decreasing rank: (a) car traffic, (b) passive smoke, (c) radon, and (d) volcano ashes. These results provide evidence that microRNA analysis can be used to retrospectively investigate the contribution of environmental factors in human lung cancer occurring in non-smokers.

Highlights

The lung epithelium undergoes a series of morphological changes before becoming invasive, such as hyperplasia, metaplasia, and dysplasia and in situ carcinoma
Our results provide evidence that miRNAs are massively deregulated in lung cancer compared with the surrounding normal tissue
A major problem in using miRNA analysis for lung cancer prediction and early diagnosis is the reproducibility of the results and the invasiveness of the biopsy approach

Summary

Introduction

The lung epithelium undergoes a series of morphological changes before becoming invasive, such as hyperplasia, metaplasia, and dysplasia and in situ carcinoma. The two main types of lung cancer are small and non-small cell lung cancer (NSCLC), accounting for 80% to 85% of all cases. It is known that microRNA and other molecular alterations (oncogene mutations, DNA adducts, transcriptional silencing activation, and proteosome alteration) induced by environmental pollution are quite specific, as each pollutant preferentially alters the expression of a cluster of identifiable molecular fingerprints [11]. This issue has been explored in a peculiar environmental situation characterized by the presence of an active volcano (Etna) near to the analyzed population (Sicily, Italy). To the best of our knowledge, the correlation between volcanic ash exposure and miRNA alterations has never been explored

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