Methylation Of The PCDH8 Promoter And Dnmt1 Expression In Gastric Cancer

Gastric cancer is a high mortality rate of malignant tumors.Most of the patients with gastric cancer have been diagnosed at an advanced stage,so the early diagnosis is very important.The carcinogenesis and progression of gastric cancer is extremely complex,involving the environmental,genetic and other aspects,among which the DNA methylation plays an important role.PCDH8(protocadherin-8),a member of the protocadherin family,has been reported as a novel tumor suppressor gene.The expression of PCDH8 gene is often reduced or silenced by aberrant promoter methylation,which is involved in several human cancers.Objective:1.To examine the methylation status of PCDH8 gene in human gastric cancer tissues and adjacent normal tissues,and to analyze the correlation between PCDH8 gene and TNM staging of gastric cancer or lymph node metastasis.2.To investigate the relationship between PCDH8 and intracellular Dnmt1.3.To analyze the biological effects of PCDH8 and Dnmt1 in the development and progression of gastric cancer.Method:Gastric cancer tissues and their corresponding adjacent tissues were collected from60 patients with gastric cancer who underwent surgical resection of Qingdao University Hospital from July 2012 to September 2013.The gastric cancer tissues were taken from the foci Central non-necrotic areas,adjacent to the tissue from the cancer tissue more than5 cm,and no preoperative radiotherapy,chemotherapy,targeted therapy and other anti-cancer treatment.The methylation status of PCDH8 gene promoter was detected by methylation-specific polymerase chain reaction(MSP),and the differences in 60 cases of gastric carcinoma and normal gastric mucosa were analyzed.The expression of PCDH8 protein and Dnmt1 protein in gastric cancer tissues and corresponding adjacent tissues were detected by immunohistochemical method.The relationship between PCDH8 andDnmt1 expression and gastric cancer was analyzed comprehensively.The expression of PCDH8 gene methylation and Dnmt1 protein in gastric cancer The relationship between the preliminary discussion.Results:Among the 60 patients,33(55.0%)showed a methylated PCDH8 promoter in samples of cancerous tissue,compared to only 2(3.3%)who showed a methylated promoter in normal samples(?2=38.76,p<0.001).Methylation status of the PCDH8 promoter showed no significant association with patient age,sex,or TNM stage.Methylation was,however,associated with lymph node metastasis(?2=17.47,p<0.001).Gastric cancer tissue showed significantly lower levels of PCDH8 protein than normal tissue(11.7% vs 90.0%,?2=73.65,p <0.001)and significantly higher levels of Dnmt1protein(73.3% vs 5.0%,?2=58.79,p <0.001).In gastric cancer samples,the level of PCDH8 protein correlated negatively with that of Dnmt1 protein(r=-0.544,p <0.001).Conclusion:PCDH8 gene is low in gastric carcinoma and DNMT1 is highly expressed in cancer tissues,indicating that it may be closely related to gastric cancer.PCDH8 gene methylation and Dnmt1 expression may be involved in the development and progression of gastric cancer.The high expression of DNMT1 protein in gastric cancer tissue may lead to abnormal methylation of the promoter region of PCDH8 gene,which may reduce the expression of tumor suppressor gene and inhibit the tumorigenesis...