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Introduction
The latest data released by the World Health Organization revealed that lung cancer has the highest global morbidity and mortality rates of all malignant tumors, and this trend is increasing yearly (1). Based on biological characteristics, treatment and prognosis, lung cancer is classified as non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC). NSCLC accounts for ~85% of all lung cancer cases, of which lung squamous cell cancer (LUSC) accounts for 20–30%, and has a five-year survival rate of <15% (2,3). With the recent rapid development of gene detection methods and targeted drugs, the overall survival time (OS) of patients with NSCLC has significantly improved (4). However, not all patients benefit from targeted therapy; in LUSC, the frequency of gene mutations sensitive to targeted drugs is relatively low, and this is accompanied by poor efficacy and the occurrence of drug resistance. In addition, the prognosis and OS of patients with early-stage lung cancer are markedly more favorable compared with those of patients at an advanced disease stage. Therefore, the identification of novel biomarkers and therapeutic targets is important for improving early diagnosis, treatment strategies and prognostic detection in patients with LUSC.
At present, the pathogenesis and progressive mechanisms of LUSC remain unclear, though the two most important mechanisms of tumorigenesis are gene mutations and epigenetic alterations (5,6). Relatively few gene mutation sites exist, particularly for early-stage patients; owing to severe fragmentization of tumor gene fragments in the blood, gene mutations are not suitable for the monitoring and diagnosis of early-stage cancer, and epigenetic changes provide a more suitable target (7,8). DNA methylation is easily detectable, and therefore the most studied, epigenetic modification, mediating the occurrence and development of cancer by regulating gene expression (8–10). It has also been indicated that DNA methylation may occur prior to gene mutation, deeming it more suitable for the early detection of cancer. Studies examining methylation and tumors have recently attracted increased attention, including a series of studies concerning targeted epigenetic therapy approaches for acute myeloid leukemia (11). Even in solid tumors, methylated or epigenetic signatures have become an area of increasing interest, in such malignancies as breast cancer (12), esophageal carcinoma (13,14), epithelial ovarian (15) and liver cancer (16). These studies indicated that the methylation of some specific...