Methylation of SOX1 and VIM promoters in serum as potential biomarkers for hepatocellular carcinoma.

PMID 28592127


Aberrant methylation of tumor-related genes has been identified as a promising biomarker for hepatocellular carcinoma (HCC). This study aimed to investigate the diagnostic value of SRY (sex determining region Y)-box 1 (SOX1) and Vimentin (VIM) promoter methylation for HCC. The study included 360 subjects, 240 patients with HCC, 29 with liver cirrhosis (LC), 66 with chronic hepatitis B (CHB) and 25 healthy controls (HCs). The methylation status of SOX1 and VIM promoters in the serum was detected by methylation-specific polymerase chain reaction (MSP). The methylation frequencies of SOX1 and VIM promoters in HCC patients were significantly higher than those in LC (p<0.001 and p<0.001), CHB (p<0.001 and p<0.001) and HC (p<0.001 and p<0.001) subjects. Furthermore, hypermethylation of SOX1 and VIM promoters were found in patients with advanced TNM stage (III-IV) and larger tumor size (≥5 cm) compared with early stage (I-II) (p<0.001 and p=0.004) patients with smaller tumor size (<3 cm) (p=0.018 and p=0.001). Moreover, the VIM promoter methylation frequency was higher in patients with portal vein tumor thrombosis (PVTT) (p=0.006) and vascular invasion (p=0.003). In addition, the combination of α-fetoprotein (≥20 ng/ml) with SOX1 and VIM promoter methylation significantly improved their diagnostic value. In conclusions, aberrant methylation of SOX1 and VIM promoters may be potential biomarkers for noninvasive detection of HCC and HCC metastasis.