Combined Methylation Analysis of SDC2 and TFPI2 in Plasma: A NoninvasiveLiquid Biopsy Approach for Early Detection of Colorectal Polyp

Document Type : Original Article

Authors
Milad Khabbazpour 1
Mohammad Heiat 2
Ashraf Karbasi 2
Majid Zaki-Dizaji 3
1 Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
2 Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
3  Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
10.22088/IJMCM.BUMS.14.2.646
Abstract
Early detection is crucial for improving survival rates in colorectal cancer (CRC). This
study evaluates the non-invasive diagnosis of polyps by assessing the methylation
status of the TFPI2 and SDC2 genes in plasma. This study enrolled 27 individuals with
low-risk polyps (LRP), 27 with high-risk polyps (HRP), and 27 healthy controls. The
quantitative methylation levels of TFPI2 and SDC2 genes were analyzed in plasma
cell-free DNA (cfDNA) using the methylation-quantification endonuclease-resistant
DNA (MethyQESD) method. Increased methylation percentages of both TFPI2
(TFPI2_1 and TFPI2_2) and SDC2 (SDC2_2) were observed in individuals with LRP
and HRP. The combination of SDC2 and TFPI2 yielded an Area Under the Curve
(AUC) of 0.732 (95% CI 0.78 to 0.96, p=0.001) with a sensitivity of 66% (95% CI
46% - 82%) and specificity of 77% (95 CI 56% - 91%) for LRP. For HRP, the AUC
was 0.890 (95% CI 0.596 to 0.843, p<0.001) with a sensitivity of 70% (95% CI 51% -
84%) and specificity of 92% (95 CI 75% - 99%). The combined assessment of SDC2
and TFPI2 methylation presents a potential approach for the early non-invasive
detection of CRC and its associated precancerous lesions
Keywords
Colorectal cancer
Methylation
plasma
polyp
SDC2
TFPI2