Expression and promoter methylation of the hypermethylated in cancer 1 gene in papillary thyroid carcinoma

Abstract

Objective To investigate the expression and promoter methylation of hypermethylated in cancer 1(HIC1) gene in papillary thyroid carcinoma and adjacent normal thyroid tissue, and its biological significance. Methods Bisulfite sequencing PCR(BSP), real-time fluorescent quantitative polymerase chain reaction(FQ-PCR) and Western blotting were used to analyze the promoter methylation and expression differences of HIC1 gene in tissues of papillary thyroid carcinoma(40 cases)and adjacent normal thyroid(40 cases). Results Compared with adjacent normal thyroid tissue (2.12±0.104, and 0.936±0.106), the expression of HIC1 m RNA and protein in papillary thyroid carcinoma was significantly decreased(0.47±0.07, and 0.417±0.071,P< 0.01). The expression of HIC1 m RNA and protein was lower in the group with lymph node metastasis(0.21±0.02, and 0.191±0.031) than in the group without lymph node metastasis(0.68±0.09, and 0.601±0.037, P<0.05).Further clinical analysis demonstrated significant association of the expression of HIC1 mRNA and protein with:age of patients(< 45 years old: 0.64±0.07, and 0.535±0.097;≥45 years old: 0.19±0.04, and 0.221±0.007), stage of disease(Ⅰ-Ⅱstage: 0.58±0.06, and 0.494±0.051;Ⅲ-Ⅳstage:0.21±0.02, and 0.237±0.023, P< 0.05).The rate of HIC1 gene promoter methylation was significantly higher(61.7%)than that in adjacent normal tissue(42.5%, P< 0.01). Conclusion Promoter hypermethylation of HIC1 in papillary thyroid carcinoma causes decreased expression of HIC1, which may be one of major reasons for the metastasis in papillary thyroid carcinoma. Key words: Hypermethylated in cancer 1; Papillary thyroid carcinoma; Methylation