Study Of Cthrc1Gene On Methylation And Expression In Epstein-barr Virus-associated Gastric Carcinoma

Epstein-Barr virus(EBV)is a gamma herpes virus and associates with multiple human tumors. DNA methylation is the most cutting-edge epigenetic mechanism. The tumor suppressor gene promoter hypermethylation is considered to be an important mechanism for the occurrence of human diseases. In the vascular remodeling process, the CTHRC1gene inhibits the TGF signaling pathway, reduces collagen deposition, promotes cell migration and expresses abnormally in many human solid tumors.Objective To detect the methylation and expression of CTHRC1gene and identify the difference of CTHRC1in positive and negative EBV-associated gastric carcinomaMethods Use the MSP and BGS methods to detect the CTHRC1gene of methylation in positive and negative EBV of gastric cancer cell lines and tissues. At the same time, we detect the CTHRC1gene expression by the real-time qPCR.Results①The MSP result of eight cell lines was the type of M+U (positive:PT, GT38, GT39and SNU719; negative:SGC7901, HGC-27, BGC-823and MKN-45). In EBV-positive gastric cancer tissues (95.4%) of the CTHRC1gene methylation was significantly higher than negative gastric cancer (38.1%).②The19of CpG sites were showed hypermethylation in8cell lines by BGS method. And there is no significant difference in part of EBVaGC and EBVnGC tisses on the degree of methylation.③The methylation level of CTHRC1gene in patients’gender, pathogenic sites, pathological classification or lymph node metastasis has no significant difference, whose P values were all greter than0.05, however, significantly different in different age groups (X2=8.972, P=0.03)。④The Δ Ctvalue of CTHRC1gene in EBV-positive and negative gastric cancer were10.30±4.24,5.36±3.60, repectively.⑤The expression level of CTHRC1gene in patients’gender, age or lymph node metastasis has no significant difference, whose P values were all greter than0.05.Conclusion①CTHRC1promoter region in EBV-positive gastric cancer tissues showed hypermethylation status, the EBV may effect the CTHRC1methylation and may be involved in EBVsGC occurrence.②CTHRC1gene differentially expressed in EBV-positive and negative gastric cancer speculated that EBV infection affect the CTHRC1expression, which may lead to the occurrence of EBVaGC.③The methylation of CTHRC1promoter region in EBV-positive was higher than EBV-negative gastric cancer tissues. And the expression of CTHRC1gene in EBV-negative was higher than EBV-positive gastric cancer tissues. It speculated that the CTHRC1gene-mediated signaling pathways may be play negatively of EBVaGC occurrence. But the role of CTHRC1gene in regulatory mechanism of EBVaGC needs to be further research.