Detection of promoter methylation status of suppressor of cytokine signaling 3 (SOCS3) in tissue and plasma from Chinese patients with different hepatic diseases

SOCS3 as an important negative regulator of IL6/JAK/STAT3 signaling pathway may be early critical determinants of carcinogenesis. This study aimed to explore the aberrant promoter methylation of SOCS3 gene in circulating DNA as a noninvasive biomarker for screening hepatocellular carcinoma (HCC) high-risk individuals and for prognosis of HCC patients after partial hepatectomy. We detected its methylation status in 116 liver tissues and 326 plasma specimens of different hepatic diseases and healthy subjects, and its mRNA and protein expression in tissues. Higher methylation rate was remarkably detected in HCC (47.92%), compared with corresponding non-tumor (25.0%), liver cirrhosis (LC) (10.0%), benign liver diseases (0%) and normal liver tissues (0%) (all P < 0.05). SOCS3 mRNA level was significantly lower in methylated HCC tissues (P < 0.05). The expressions of SOCS3 and pSTAT3 were affected by methylation status. Correlation and consistency of SOCS3 methylation were found between cancer tissue and corresponding plasma (P < 0.001, kappa = 0.747). The detection rate of plasma for HCC reached 73.91%, with no false positive error. SOCS3 methylation status both in tissue and plasma was significantly associated with AFP400, tumor size, tumor differentiation, LC, metastasis and recurrence (all P < 0.05). Patients with SOCS3 methylation were followed up a markedly poorer prognosis than those unmethylated for disease-free survival (P < 0.05). These data indicate that methylation status of SOCS3 in plasma cell-free DNA can correctly reflect that in tissue DNA and be used as a noninvasive potential biomarker for chronic liver disease monitoring, predicting the degree of malignancy and poor prognosis of HCC.