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Diagnostic value in colorectal tumorous lesions of SDC2/TFPI2 methylation based on bowel subsite difference

By Lianglu Zhang, Lanlan Dong, Changming Lu, Wenxian Huang, Cuiping Yang, Qian Wang, Ruixue Lei, Rui Sun, Kangkang Wan, Tingting Li, Fan Sun, Tian Gan, Jun Lin, Lei Yin

Posted 24 Feb 2021
medRxiv DOI: 10.1101/2021.02.22.21252188

BackgroundSDC2 methylation is a potential biomarker for colorectal cancer detection with specificity over 90%, but its sensitivity is usually less than 90%. The study aims to improve the sensitivity and specificity by adding TFPI2 methylation as a complement. MethodsTFPI2 was identified using colorectal cancer samples from TCGA database with SDC2 methylation level lower than 0.2. SDC2/TFPI2 methylation specific PCR was performed using tissue samples (184 cancer and 54 healthy control) and stool samples (289 cancer, 190 adenoma and 217 healthy control). Detection sensitivity was calculated among tumors from different biopsy locations. Results88% of 50 TCGA specimens of colorectal cancer with SDC2 methylation level lower than 0.2 showed TFPI2 methylation level higher than 0.2. SDC2/TFPI2 combined detection in stool specimens showed AUC value of 0.98 with the specificity of 96.40% and sensitivity of 96.60% for cancer vs control, AUC value of 0.87 with the specificity of 95.70% and sensitivity of 80.00% for adenoma vs control. The sensitivities were much higher than those of SDC2, and the improvement was most significant in lesions from left colon and rectum. ConclusionsThis research indicated that the addition of TFPI2 can reduce the miss detection rate of colorectal cancer and adenomas while maintaining high specificity, probably by finding neoplasms in left colon.The method is non-invasive and has good compliance, also avoiding the pain of bowel preparation and risk of cross infection during endoscopy, so it will provide an easy and precise tool for colorectal cancer and its precancerous lesions screening.

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