| ObjectiveAberrant promoter methylation of tumor suppressor genes is one of the important mechanisms of epigenetics, which participate the occurrence and development of gastric cancer. In this study, methylation-specific polymerase chain reaction and bisulfite sequence polymerase chain reaction (BSP) methods were used to detect promoter methylation status of RUNX3 and CHFR genes in cancer tissues from gastric cancer patients. These patients were follow-up after surgical resections, and the relationship between methylation status of the two genes and clinicopathological features and survival duration after surgical resections was analyzed.MethodsA total of 123 patients diagnosed as primary gastric cancer through pathobiology and without receiving any radiotherapy or chemotherapy before operation were collected. During their surgical resection, the carcinoma specimens were taken from the center of cancer tissues, and thirty benign gastric mucosae were collected as control group. Methylation-specific polymerase chain reaction (MSP) and bisulfite sequence polymerase chain reaction (BSP) methods were used to detect the promoter methylation status of RUNX3 and CHFR genes from these specimens. The patients were followed up to get message of live time. Survival curves were calculated according to Kaplan-Meier method and compared with the use log-rank test. Multivariate analysis was based on backward Cox regression model . Prognosis multivariate analysis using Cox proportional hazard model. Results1. In gastric cancer tissues, the methylation frequencies of RUNX3 and CHFR genes were found to be 54.4% and 41.4% respectively, while in benign gastric mucosae, they were both found to be 0, the methylation frequencies of the two genes in cancer tissues were significantly higher than that in benign gastric mucosae (P<0.05).2.The methylation frequencies of RUNX3 and CHFR genes were found to be 62.7% and 49.3% in cancer tissues with tumor size≥5cm, and in cancer tissues with tumor size <5cm, they were 41.7% and 29.2%, respectively. The frequencies of RUNX3 and CHFR methylation in tumor size≥5cm were significantly higher than those in tumor size <5cm (PRUNX3 = 0.023, PCHFR = 0.027). In cancer tissues with stage T3/T4 and T1/T2, the frequencies of RUNX3 methylation were 62.2% and 33.3% respectively, the former was significantly higher than the latter. In cancer tissues with stage G3/G4 and G1/G2, the methylation frequencies of CHFR were 50.0% and 25.6% respectively, the former was significantly higher than the latter. No significant relationship was found between RUNX3 and CHFR methylation and other clinicopathological features including the age, gender, stage of pathology and the involvement of lymph node (P>0.05).3.The survival duration after surgical resections in patients with methylated CHFR was significantly shorter than that in patients with unmethylated CHFR (PCHFR = 0.03), while no significantly result was found between RUNX3 methylation status and survival duration after surgical resections in gastric cancer patients (P = 0.27). The median survival time of gastric cancer patients with tumor size < 5cm was significantly longer than those with tumor size≥5cm (P=0.04). There were no significant associations between other factors such as age, sex, tumor differentiation, the involvement of lymph node, stage of pathology and tumor invasion depth and the median survival time of gastric cancer patients.Conclusions1. Aberrant promoter methylation of RUNX3 and CHFR genes were significantly associated with the clinicopathological features of gastric cancer patients and played important roles in the occurrence and development of gastric cancer.2. The survival duration after surgical resections in patients with methylated CHFR was significantly shorter than those with unmethylated CHFR, suggesting that the methylation status of CHFR could use as a biomarker for the prediction of survival duration after surgical resections in gastric cancer.
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