DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma

Jin Huang,1,2 Zhi-Rong Tan,1,2 Jing Yu,1,2 He Li,1,2 Qiao-Li Lv,1,2 Ying-Ying Shao,3 Hong-Hao Zhou1,2 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan, 3Institute of Life Science, Chongqing Medical University, Yuzhong District, Chongqing, China Background: Colorectal cancer (CRC) is a widespread and aggressive carcinoma with poor prognosis. Hypermethylation of specific gene promoters is an important mechanism of CRC. In this study, we investigated the hypermethylation of paired boxed gene 1 (PAX1) and sex-determining region Y-related high-mobility group box 1 (SOX1) genes in CRC tissues. Methods: DNA methylation at cg2,09,07,471 PAX1 and cg0,66,75,478 SOX1 from 166 cancer tissues and 37 normal tissues from CRC patients were compared using datasets downloaded from The Cancer Genome Atlas. Quantitative methylation-specific polymerase chain reaction and assay of PAX1 and SOX1 were performed in dissected tumor and paracancerous tissues by surgery from 41 CRC patients. Quantitative reverse transcription polymerase chain reaction and immunohistochemistry assay were performed in both CRC and paired normal tissues to detect mRNA and protein expression, respectively.Results: Methylation levels of PAX1/SOX1 genes were significantly higher in cancer tissues than in paired normal tissues. PAX1 and SOX1 genes were methylated in 28 (68.3%) of the 41CRC samples but in 5 (12.2%) and 0 (0%) of the paired normal control samples (both P0.5). In addition, the methylation level of PAX1/SOX1 was significantly higher in CRC patients with high TNM stage (TNM stage III/IV, 3.11±2.43) than those with low TNM stage (TNM stageI/II, 1.26±2.94, P