Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Sep 27, 2023; 15(9): 2032-2041
Published online Sep 27, 2023. doi: 10.4240/wjgs.v15.i9.2032
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
Ji Hyeong Song, Jin Soo Kim, Department of Surgery, Chungnam National University Sejong Hospital, Sejong 30099, South Korea
Tae Jeong Oh, Sungwhan An, Genomictree, Inc., Daejeon 34027, South Korea
Kyung Ha Lee, Ji Yeon Kim, Jin Soo Kim, Department of Surgery, College of Medicine, Chungnam National University, Daejeon 35015, South Korea
Author contributions: Song JH collected and analyzed the clinical data, drafted the manuscript, and prepared the figures; Oh TJ and An S drafted the manuscript; Lee KH and Kim JY collected the stool samples; Kim JS participated in study design, collected the stool samples, collected and analyzed the clinical data, drafted the manuscript, and prepared the figures; All authors read and approved the final manuscript.
Supported by the Research Fund of Chungnam National University, No. 2018-0626-01.
Institutional review board statement: This observational study was approved by the Institutional Review Board of our institute (IRB No. 2016-05-018).
Informed consent statement: Written informed consent was obtained from all subjects.
Conflict-of-interest statement: The authors declare that they have no competing interests.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Corresponding author: Jin Soo Kim, MD, PhD, Assistant Professor, Surgery, Chungnam National University Sejong Hospital, 20, Bodeum 7-ro, Sejong-si, Republic of Korea, Sejong 30099, South Korea. jskim7562@gmail.com
Received: June 8, 2023
Peer-review started: June 8, 2023
First decision: July 7, 2023
Revised: July 13, 2023
Accepted: August 4, 2023
Article in press: August 4, 2023
Published online: September 27, 2023
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 (CT) 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, DNA methylation, Syndecan-2, Colorectal cancer

Core Tip: This prospective study evaluated the detection of syndecan-2 (SDC2) methylation in preoperative and postoperative stool DNA samples of colorectal cancer (CRC) patients. The study demonstrated that the SDC2 methylation test showed high sensitivity (88.6%) for detecting CRC before surgery, indicating its potential as a non-invasive diagnostic tool. Postoperatively, the detection rate decreased to 19.7%, suggesting the normalization of SDC2 methylation after surgical resection. The study highlights the diagnostic value of SDC2 methylation in preoperative and postoperative stool samples, supporting its role as a non-invasive screening tool for CRC.