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Introduction
Lung cancer has continued to be the most common type of cancer worldwide for several decades, with the highest incidence and mortality rates (1). Only 13% of patients with lung cancer survive for >5 years (2). As the second leading risk factor for lung cancer, asbestos exposure is responsible for an estimated 5–7% of all these cancers (3). Asbestos-related lung carcinoma is considered to be one of the most devastating occupational cancers (4). Although the use of asbestos has been banned or severely restricted since the early 1970's in many developed countries, asbestos-related lung cancer still poses a great public health threat due to the long latency period from asbestos exposure to the incidence of asbestos-induced cancer (5).
It has been widely accepted that early detection and precise diagnosis of cancer subtypes could greatly enhance the efficacy of targeted therapies and improve disease outcome, and in fact, markedly increase the patient survival rate (6). To date, many imaging and cytology-based methods have been applied for early detection (7–9). However, most techniques have limited sensitivity to detect asbestos-related lung cancer, as the histopathological subtypes of lung cancer patients with and without asbestos exposure are quite similar (10).
Among asbestos-related lung cancer, non-small cell lung cancer (NSCLC) accounts for at least 80% of these cases (2). There are three primary subtypes of NSCLC distinguishable by the appearance and chemical makeup of the cells: adenocarcinoma (LC-AC), squamous cell carcinoma (LC-SCC) and large-cell carcinoma. It has been shown that gene expression profiles could be used to distinguish asbestos-exposed from non-exposed lung cancer patients (11). Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines have revealed that the expression levels of genes such as nuclear factor-κB (NF-κB) subunit 2 (NFKB2), IKBKB, thioredoxin (TXN), thioredoxin reductase (TXNRD1), BCL2 interacting protein 3 like (BNIP3L), protein kinase C (PKC)δ and adducin (ADD)3 were significantly altered in response to asbestos exposure in all the cell lines (12). Moreover, accumulating in vivo and in vitro studies have identified asbestos-related gene expression changes involved in activation of the NF-κB pathway, p53 promoter activation, MAPK signaling pathway and cell proliferation induced by tumor necrosis factor-α (TNF-α) and TNF-β as well as PDGFA and PDGFB (13,14). The increase in available tumor samples of patients...