Comparative detection of syndecan-2 methylation in preoperative and postoperative stool DNA in patients with colorectal cancer

Ji Hyeong Song; Tae Jeong Oh; Sungwhan An; Kyung Ha Lee; Ji Yeon Kim; Jin Soo Kim

doi:10.4240/wjgs.v15.i9.2032

Comparative detection of syndecan-2 methylation in preoperative and postoperative stool DNA in patients with colorectal cancer

World J Gastrointest Surg. 2023 Sep 27;15(9):2032-2041. doi: 10.4240/wjgs.v15.i9.2032.

Authors

Ji Hyeong Song¹, Tae Jeong Oh², Sungwhan An², Kyung Ha Lee³, Ji Yeon Kim³, Jin Soo Kim^{1

4}

Affiliations

¹ Department of Surgery, Chungnam National University Sejong Hospital, Sejong 30099, South Korea.
² Genomictree, Inc., Daejeon 34027, South Korea.
³ Department of Surgery, College of Medicine, Chungnam National University, Daejeon 35015, South Korea.
⁴ Department of Surgery, College of Medicine, Chungnam National University, Daejeon 35015, South Korea. jskim7562@gmail.com.

Abstract

Background: Early detection of colorectal cancer (CRC) is essential to reduce cancer-related morbidity and mortality. Stool DNA (sDNA) testing is an emerging method for early CRC detection. Syndecan-2 (SDC2) methylation is a potential biomarker for the sDNA testing. Aberrant DNA methylation is an early epigenetic event during tumorigenesis and can occur in the normal colonic mucosa during aging, which can compromise the sDNA test results.

Aim: To determine whether methylated SDC2 in sDNA normalizes after surgical resection of CRC.

Methods: In this prospective study, we enrolled 151 patients with CRC who underwent curative surgical resection between September 2016 and May 2020. Preoperative stool samples were collected from 123 patients and postoperative samples were collected from 122 patients. A total of 104 samples were collected from both preoperative and postoperative patients. Aberrant promoter methylation of SDC2 in sDNA was assessed using linear target enrichment quantitative methylation-specific real-time polymerase chain reaction. Clinicopathological parameters were analyzed using the results of SDC2 methylation.

Results: Detection rates of SDC2 methylation in the preoperative and postoperative stool samples were 88.6% and 19.7%, respectively. Large tumor size (3 cm, P = 0.019) and advanced T stage (T3-T4, P = 0.033) were positively associated with the detection rate of SDC2 methylation before surgery. Female sex was associated with false positives after surgery (P = 0.030). Cycle threshold (C_T) values were significantly decreased postoperatively compared with preoperative values (P < 0.001). The postoperative negative conversion rate for preoperatively methylated SDC2 was 79.3% (73/92).

Conclusion: Our results suggested that the SDC2 methylation test for sDNA has acceptable sensitivity and specificity. However, small size and early T stage tumors are associated with a low detection rate of SDC2 methylation. As the cycle threshold values significantly decreased after surgery, SDC2 methylation test for sDNA might have a diagnostic value for CRC.

Keywords: Biomarkers; Colorectal cancer; DNA methylation; Syndecan-2.