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

Abstract

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.

HDNA methylation data-based molecular subtype classification related to the prognosis of patients with hepatocellular carcinoma

“…The low methylation of genes such as AKT3, CD147, LINE1 and SFRP1 has been proven to be significantly correlated with the survival, tumour volume and malignant grade of HCC patients [ 12 – 14 ]. Moreover, the silencing of tumour suppressor genes and the loss of DNA repair function in HCC are closely correlated with the high methylation of promoter CpG islands, which prevents the timely repair of DNA damage, thus resulting in abnormal cell proliferation; for instance, the CpG islands of genes such as SOX1, VIM, BMP4 and CDKN2A show high methylation levels [ 15 – 17 ]. However, it is still unknown whether specific methylation patterns in these gene promoter regions display clinical significance compared with tumour classification, survival and prognosis in large-sample HCC patient data.…”

MiR-155-5p Suppress SOX1 to Promote the Proliferation of Cholangiocarcinoma via RAF/MEK/ERK Pathway

“…SOX1 is a member of the transcription factor sox family, which plays an important role in embryo and postnatal development. According to the current research, SOX1 also has a certain inhibitory effect on a variety of tumors, and many studies have proved that SOX1 can be used as a biomarker for a variety of tumors, such as cervical cancer, colon cancer, glioma, liver cancer, ovarian cancer, small cell lung cancer (24)(25)(26)(27)(28)(29), etc. But association between SOX1 and CCA has not been reported.…”

SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis

“…For instance, SOX1 methylation is associated with liver cancer, and SOX1 promoter methylation level is significantly higher in patients with high TNM stage (stages III and IV) than in those with low TNM stage. The SOX1 methylation level is significantly higher in liver cancer patients with large tumor size (≥5 cm) than in those with small tumor size (<3 cm) (Liu et al, 2017 ). In addition, SOX1 methylation is a useful biomarker for oral squamous cell carcinoma (Cheng et al, 2016 ) and CC screening (Huang et al, 2017 ).…”