Significance of combined detection of peripheral blood free Septin9 SDC2 and BCAT1 gene methylation in the diagnosis of colorectal cancer / 中华检验医学杂志

ABSTRACT

Objective:To explore the clinical significance of combined detection of the promoter methylation of plasma free Septin9, SDC2 and BCAT1 genes in peripheral blood for the diagnosis of colorectal cancer. Methods The data of patients admitted to the Department of Gastroenterology, Shanghai East Hospital Affiliated to Tongji University from January to September 2019 were retrospectively analyzed. They were divided into colorectal cancer group (62 cases of colon cancer, 59 cases of rectal cancer), precancerous lesions group (77 cases of colorectal adenoma, 5 cases of high-grade intraepithelial neoplasia), interference group (61 cases of colorectal cancer and advanced adenoma negative but suffered other intestinal lesions, 17 cases of non-colorectal cancer) and healthy group (94 cases). The methylation status of three genes (Septin9, SDC2 and BCAT1) in peripheral blood plasma was detected simultaneously by fluorescence PCR. The relationship between the positive rate of three genes detected jointly and the clinic pathological characteristics of colorectal cancer was analyzed and compared with serum carcinoembryonic antigen (CEA) positive rate. The colorectal cancer group was divided into stage Ⅰ, Ⅱ, Ⅲ and Ⅳ according to TNM stage, and the colorectal cancer group was analyzed and counted by grade. The diagnostic efficiency of detection methods was analyzed by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was compared.Results:The positive rate of combined detection of SDC2 and BCAT1 gene methylation was higher than other three groups (χ 2 =237.246, P<0.001). The positive rate of combined detection of plasma Septin9, SDC2 and BCAT1 gene methylation was higher than CEA in colorectal cancer group ( P<0.001). The positive rates of the combined detection of plasma Septin9, SDC2 and BCAT1 gene methylation in stage Ⅰ-Ⅳ of colorectal cancer group were 73%(16/22), 87%(34/39), 86%(30/35) and 96%(24/25), respectively. Compared with CEA group, the positive rate of combined detection of plasma Septin9, SDC2 and BCAT1 gene methylation in stage Ⅰ-Ⅲ of colorectal cancer group was higher than serum CEA ( P<0.001), but the positive rate of stage Ⅳ was not statistically significant compared with CEA group ( P>0.05). ROC curve analysis showed that the AUC of Septin9, SDC2 and BCAT1 was 0.857(95% CI 0.810-0.903),0.819(95% CI 0.768-0.871)and 0.862(95% CI 0.816-0.909), respectively. The AUC of combined detection of three gene methylations was 0.889 (95% CI 0.846-0.933), and the AUC of combined detection with serum CEA was 0.913 (95% CI 0.874-0.951). There was no significant difference in the positive rate of combined detection of Septin9, SDC2 and BCAT1 gene methylation among different gender, age and cancerous site of colon cancer patients (all P>0.05). Conclusion:The combined detection of the promoter methylation of plasma free Septin9, SDC2 and BCAT1 genes in peripheral blood plasma is helpful for the early diagnosis of colorectal cancer. The positive rate in stage Ⅰ-Ⅲ of colorectal cancer group is higher than serum CEA. The combined diagnosis of the three genes can improve the diagnostic efficiency.