TGFB2 and BCL2L11 methylation in male laryngeal cancer patients

Abstract

Abstract. DNA methylation is a major regulatory mechanism of gene expression. The aim of the present study was to test the association of transforming growth factor β2 (TGFB2) and B cell lymphoma 2-like 11 (BCL2L11) gene methylation with the risk of laryngeal squamous cell carcinoma (LSCC). Using bisulfite pyrosequencing technology, DNA methylation levels of TGFB2 promoter and BCL2L11 gene-body CpG cytosines were measured in 90 LSCC tissues and 90 adjacent normal tissues. Analysis of variance and paired sample t-test were used to determine the association of gene methylation and the risk of LSCC. Our results revealed that there were no differences in TGFB2 and BCL2L11 methylation levels between the LSCC tissues and the paired normal tissues (P>0.05). Further breakdown analyses demonstrated that the association results of the two gene methylation levels and LSCC remained unchanged with the age, smoking history, histological differentiation or clinical stage of the LSCC patients (all adjusted P>0.05). In conclusion, there is no association of TGFB2 promoter and BCL2L11 gene-body methylation with the risk of LSCC in males. IntroductionLaryngeal squamous cell carcinoma (LSCC) is the second most common head and neck cancer in the world (1). The incidence of LSCC in China has exhibited an increasing trend in the young population (2,3). LSCC is a complex disease, and it is hypothesized that both genetic and environmental factors play a role in it (4). Epigenetic modifications, including DNA methylation, are known as the bridging factors of genetics and the environment (5). However, the role of epigenetic modifications in the pathogenesis and progression of LSCC remains to be explained.DNA methylation of CpG islands (CGIs) is a significant regulatory mechanism of gene expression (6). Epigenetic silencing of tumor suppressor genes by promoter hyper methylation is considered to be a significant event in the progression of cancers including leukemia (7), lung cancer (8) and prostate cancer (9). Gene-body methylation levels are also demonstrated to be correlated with gene expression (10,11).TGFB2 is a member of the transforming growth factor β (TGFB) family, which encodes multifunctional peptides in the regulation of cell proliferation, differentiation, adhesion and migration (12). TGFB is able to inhibit tumor growth at the early stages and promote tumor growth at the late stages of disease (13). A previous study has demonstrated that increased TGFB2 promoter methylation level is associated with prostate cancer progression (14). BCL2L11 encodes a member of the BCL-2 (B cell lymphoma 2) protein family, which acts as an apoptotic activator that is involved in a wide variety of cellular activities (15). BCL2L11 methylation has been noted to be associated with the risk of hematological and epithelial cancers (16).In the current study, the methylation levels of TGFB2 and BCL2L11 were investigated in male laryngeal cancer patients to determine whether these epigenetic markers are associated with LSCC risk. Materials and methods

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