The Diagnostic Significance Of SOCS3 Promoter Methylation And Its Correlation With IDH1 Mutation In Chinese Glioma Patients

Glioma is the most common malignant tumor in the central nervous system, with rapid progression,short-term survival and difficult to cure. In recent years, concept of biomarker appeared. Biomarkers can help clinical diagnosis and prognosis prediction for glioma and make up for the insufficient that traditional pathological grading and classification cannot predict clinical prognosis. On the basis of cancer genomics and molecular genetics, pathological molecular typing can identify mixed tumors that traditional diagnostic methods are difficult to. Therefore, screening biomarkers for glioma treatment and prognostic is quiet important.SOCS3 is a key negative regulator of JAK-STAT signaling pathway and considered to be a tumor suppressor gene. Studies showed that SOCS3 promoter methylation status has differentiation among different pathological grades and types of glioma. SOCS3 methylation level was lower in WHO Ⅳ grade than that in WHO Ⅱ, Ⅲ grade in glioma. Compared other glioma types, glioblastoma has lower SOCS3 promoter methylation status. Patients with differentiated SOCS3 promoter methylation status have different prognosis.In this paper, we defined 5 CpG sites which could be on behalf of SOCS3 promoter region methylation and have the potential to be used as a biomarker. We detected methylation levels of the 5 CpG sites and IDH1 R132H mutation in 51 glioma samples with different grades and types by pyrosequencing. We also detected SOCS3 mRNA expression levels via real-time quantitative reverse transcription PCR (qRT-PCR) method. The results showed that SOCS3 promoter methylation degree was lower in WHO IV samples than that in WHOⅢ, and oligodendrocytes astrocytoma group had higher SOCS3 promoter methylation degree than glioblastoma did. After data analysis, we concluded that SOCS3 methylation status was significantly correlated with its mRNA expression level inversely and performed a lower expression in unmethylated group. We firstly found IDH1 R132H mutation can significantly increase SOCS3 promoter methylation.In conclusion, SOCS3 may be as a potential biomarker for glioma grading, classification and prognosis, and we still require plenty of evidence and data to support. Our study will provide a certain amount of evidence and data basis for SOCS3 biomarker research.