Abstract
To evaluate the applicability of bisulfate conversion-free methylation assay based on enzyme digestion in fecal screening for colorectal cancer (CRC). Stool samples were collected from a total of 1142 participants with intestinal abnormalities, including 180 positive cases, 60 advanced adenomas, and 902 negative cases. DNA from reference cell lines and clinical samples was extracted and digested with an enzyme to detect the methylation of CRC markers SEPT9, SDC2, NDRG4, SFRP2, and BMP3 genes. Statistical analysis was then used to determine the ability of the markers, both individually and in combination, to detect CRC and adenoma. Our results showed that the enzyme digestion method could suitably detect DNA marker methylation in as low as 1% of the cell lines. BMP3 had a considerably low detection rate in all clinical samples, with only 6 positive cases detected out of 180 cancer samples. Our findings showed that the combination of SEPT9, SDC2, and SFRP2 had an area under the receiver operation curve of 0.937, sensitivity of 94.11%, and specificity of 89.21% for detecting CRC. Moreover, the detection sensitivity of adenoma can also reach 38.33%. After innovatively utilizing bisulfate conversion-free methylation assay for CRC screening, this study verified the potential clinical applicability of combining multiple biomarkers for CRC screening in a large number of samples.
Highlights
Colorectal cancer (CRC), the third most common type of malignancy in Western countries, has continued to rapidly increase in developing countries [1,2,3]
With each marker as an independent factor influencing the results, models were used to comprehensively evaluate the cumulative effect in CRC prediction, and the results showed that area under the ROC curve (AUC) and sensitivity reached their maximum when three markers, septin 9 (SEPT9), syndecan 2 (SDC2), and secreted frizzled-related protein 2 (SFRP2), were used (Figure 5)
Available fecal DNA methylation analyses have been used for CRC screening due to their noninvasive and highly sensitive characteristics
Summary
Colorectal cancer (CRC), the third most common type of malignancy in Western countries, has continued to rapidly increase in developing countries [1,2,3]. Colonoscopy has remained the gold standard method for the clinical screening of CRC despite being an invasive procedure with certain risks, such as bleeding and anesthesia, troublesome pretreatment, and some contraindications, causing low acceptance among patients [8,9,10]. Noninvasive detection methods, such as fecal immunochemical tests for hemoglobin and imaging, have displayed low sensitivity and specificity, which could cause false positive or false negative results especially in the detection of colorectal adenomas or stage I CRCs [11,12,13]. There is an urgent need for a noninvasive, convenient, rapid, sensitive, and specific screening method for CRC and its precancerous lesions
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