| Objective Nowadays,The incidence and mortality rate of colorectal cancer(CRC)continue to rise,ranking the third among malignant tumors and seriously affecting human health.The early diagnosis and treatment of colorectal cancer and its precancerous lesions can significantly reduce the mortality.At present,the gold standard for colorectal cancer screening and diagnosis is colonoscopy.However,due to its complex intestinal preparation and the risk of intestinal bleeding and perforation,the compliance of the general risk population of colorectal cancer is low.Therefore,there is an urgent need for a simple,safe and noninvasive screening method for the early diagnosis of colorectal cancer and its precancerous lesions.CRC is the result of abnormal gene expression,progressive accumulation of abnormal substances and continuous stimulation by high-intensity carcinogenic factors,and abnormally expressed genes may become a biological marker for monitoring the development of colorectal cancer and evaluating its efficacy.The increasing maturity of gene detection technology and the development of bioinformatics have shown that the methylation of some genes can be applied to the early diagnosis,treatment and prognosis monitoring of colorectal cancer.Some analytical methods have been commercialized and written into clinical guidelines to guide clinical practice.To investigate the methylation status of SDC2,PPP2R5C and ADHFE1 genes in feces and their value in the screening of colorectal cancer and precancerous lesions.Methods the morning stool samples of 64 patients with colorectal cancer,72 patients with adenoma,33 patients with proliferative polyps and 59 healthy people from Oncology department and digestive department of Qingdao Central Hospital Affiliated to Qingdao University from August 1st 2020 to March 1st 2021 were collected.The target gene DNA was extracted and modified with bisulfite.The methylation status of SDC2,PPP2R5C and ADHFE1 genes were detected by methylation specific polymerase chain reaction(qMSP).Taking the pathological results as the gold standard,the value of combined detection of methylation of three genes and fecal occult blood test(FOBT)in the diagnosis of colorectal cancer and precancerous lesions was compared through receiver operating characteristic(ROC)curve and area under curve(AUC).To construct a prediction model of DNA methylation detection for colorectal cancer was constructed.Results the positive rates of the classification model based on the methylation status of fecal SDC2,PPP2R5C and ADHFE1 genes were higher than those of FOBT in colorectal cancer[90.63%(58/64)vs 70.31%(45/64),P=0.003],adenoma[59.72%(43/72)vs 26.39%(19/72),P=0.002],and proliferative polyps[21.21%(7/33)vs 6.06%(2/33),P=0.125].There was no significant difference in the positive rate between healthy controls[10.17%(6/59)and 8.47%(5/59),P=1.000].The methylation state model was better than FOBT in the diagnosis of colorectal cancer and adenoma(AUC:0.85 vs 0.71,P<0.001),especially in the diagnosis of adenoma(AUC:0.82 vs 0.64,P<0.001).The methylation status of ADHFE1 has the highest sensitivity in the diagnosis of colorectal cancer,and the methylation status of SDC2 has high accuracy in the diagnosis of adenoma and colorectal cancer.In colorectal cancer patients over 50 years old,the positive rate according to methylation status model was higher than FOBT(68.9%(42/61)vs 90.2%(55/61),P<0.05).Conclusion1.Compared with traditional fecal occult blood detection,multi-target fecal DNA methylation has higher diagnostic rate and specificity.It is expected to become a simple,noninvasive and safe biomarker for early diagnosis of colorectal cancer.2.The combined detection of multi-target fecal DNA methylation has a certain value for the early diagnosis of colorectal adenoma and helps to screen precancerous lesions.3.The methylation status of ADHFE1 is highly sensitive in detecting colorectal cancer,and the methylation status of SDC2 is highly accurate in detecting adenoma and colorectal cancer. |
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