ABSTRACT
Objective:To detect the methylation status of sine oculis homeobox homolog1 (Six1) in patients with gastric cancer and analyze its relationship with the clinicopathological characteristics and prognosis of patients.Methods:The tumor and para-cancerous tissues of 148 patients with gastric cancer diagnosed and treated in Aerospace Center Hospital from September 2015 to December 2017 were collected. The methylation-specific PCR method (MSP) was used to detect the methylation status of the Six1 gene, and 100 normal people who underwent gastroscopy biopsy during the same period served as the control group. Univariate analysis and multivariate Logistic regression model were used to analyze the relationship between Six1 methylation status and clinical pathological characteristics of patients. Kaplan-Meier survival curve was used to analyze the relationship between Six1 methylation status and prognostic survival in patients with gastric cancer.Results:Six1 gene methylation rate in tumor tissue was lower than that in adjacent tissues or in control group, and the differences were statistically significant: 24.32%(36/148) vs. 89.19%(132/148), 96.00%(96/100)( P<0.05). Univariate analysis showed that Six1 gene methylation rate was higher in patients with tumor diameter <5 cm ( χ2 = 8.79, P = 0.003), TNM stage Ⅰ-Ⅱ ( χ2 = 4.93, P = 0.026), highly differentiated tumor ( χ2 = 8.74, P = 0.013), no lymph node metastasis ( χ2 = 4.64, P = 0.031), no distant metastasis ( χ2 = 4.38, P = 0.036), and no invasion of the serosa ( χ2 = 9.85, P = 0.002), and the differences were statistically significant. Multivariate analysis showed that TNM staging ( OR = 4.397, 95% CI 3.141 - 5.157, P = 0.014), tumor differentiation ( OR = 4.491, 95% CI 3.527 - 6.118, P = 0.007), lymph node metastasis ( OR = 4.208, 95% CI 3.823 - 5.195, P = 0.031), distant metastasis ( OR = 4.225, 95% CI 3.956 - 5.437, P = 0.026), and depth of invasion ( OR = 4.509, 95% CI 3.206 - 5.275, P = 0.011) of patients with gastric cancer were independent risk factors for Six1 gene methylation status. Till to March 2020, the mortality rate of the Six1 gene methylation group was lower than that of the Six1 gene unmethylated group: 44.44%(16/36) vs.71.43% (80/112), the difference was statistically significant ( χ2 = 8.70, P<0.05). The median survival time of gastric cancer patients with Six1 gene methylation was higher than that of Six1 gene unmethylated (49 months vs. 37 months), and the difference was statistically significant ( P = 0.019). Conclusions:There is unmethylation of Six1 gene in patients with gastric cancer, which may be involved with the occurrence of gastric cancer. Patients′ TNM stage, tumor differentiation degree, and lymph node metastasis are independent risk factors for Six1 gene methylation status in gastric cancer patients. The prognosis of gastric cancer patients with Six1 gene methylation is better.