IL10 hypomethylation is associated with the risk of gastric cancer

Abstract

Interleukin-10 (IL10), a pleiotropic cytokine secreted by type-2 helper (Th2) T cells, contributes to the oncogenic activation or inactivation of tumor-suppressor genes. The present study investigated whether hypomethylation of IL10 CpG island (CGI) was associated with the risk of developing gastric cancer (GC) and the prognosis of patients with GC. A fragment (hg18, chr1: 206945638-206945774) at the CGI of IL10 was selected for the present methylation assay. Quantitative methylation-specific PCR was used to evaluate the methylation of IL10 CGI in 117 tumor samples from patients with GC. The results demonstrated that IL10 CGI methylation was significantly lower in the tumor tissues compared with that in the paired adjacent non-tumor tissues (median percentage of methylated reference, 29.16 vs. 42.82%, respectively; P=4×10 −8 ). Furthermore, results from receiver operating characteristic curve analysis identified a significant area under the curve of 0.706, with a sensitivity and a specificity of 77.8 and 58.1%, respectively, between cancer tissues and paired adjacent non-tumor tissues. Furthermore, the methylation of IL10 CGI was significantly associated with patients' age at diagnosis (r=−0.201; P=0.03). Subgroup analyses demonstrated that the association between IL10 CGI hypomethylation and the risk of GC was specific for patients with low differentiation (P=1×10 −7 ) and Borrmann types III+IV (P=1×10 −7 ). In addition, IL10 CGI hypomethylation was significantly associated with the risk of GC for patients without smoking history (P=3×10 −7 ) or a family history of cancer (P=2×10 −7 ). The results from Kaplan-Meier survival analysis demonstrated that IL10 CGI hypomethylation was associated with a significantly shorter overall survival of patients with GC (P=0.041). Similar results were identified for patients with GC who did not have smoking history (P=0.037) or a family history of cancer (P=0.049). The results from this study demonstrated that IL10 CGI hypomethylation may be considered as a potential biomarker for the diagnosis and prognosis of patients with GC in the Chinese population.

Screening of Active Components and Key Targets of Radix Codonopsis in the Treatment of Gastric Cancer

“…IL-10 is a multidirectional cytokine that can regulate tumor suppressor gene. e methylation rate of a CGI fragment of the IL-10 gene in tumor patients was obviously lower than that in normal cells, and the methylation of IL-10 was related to gastric cancer [21]. rough screening, we have obtained that the key active components of Radix Codonopsis in the treatment of gastric cancer are C9-luteolin and C32-cryptotanshinone.…”

New biomarker: the gene HLA-DRA associated with low-grade glioma prognosis

“…The protein–protein interactome (PPI) network explored the network relationship between survival genes and used Cytoscape for visualization. Significantly high network nodes, IL10, CCL2, CD74, and HLA-DRA, were found to be responsible for tumorigenesis, macrophage enrichment, and immune response among others [ 36 – 38 ]. Thirty-eight prognostic genes were obtained by the COX analysis, and then, the top five genes with the most nodes were selected from the PPI network.…”

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions

“…Additionally, hypomethylation was found in oncogene promoters such as MN/CA9 in human renal cell carcinoma [56], and multidrug resistance 1 (MDR1) in invasive ductal breast carcinoma [12]. It has also been found in IL-10 CGI, a cytokine that contributes to the oncogenic activation and inactivation of tumor suppressor genes in gastric cancer [57].…”