Circulating DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer

Abstract Plasma DNA methylation SEPTIN9, Syndecan 2 (SDC2), and Branched Chain Amino Acid Transaminase 1 (BCAT1) tests have served as valuable diagnostic, prognostic, and predictive markers for colorectal cancer (CRC). In this study, we analyzed data including 104 eligible CRC patients, 138 colorect...

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Main Authors: Beibei Chen, Huan Zhao, Huihui Hu, Haili Shang, Hui Wang, Zhentao Yao, Jinxi Huang, Huifang Lv, Weifeng Xu, Jianzheng Wang, Caiyun Nie, Jing Zhao, Yunduan He, Saiqi Wang, Xiaobing Chen
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Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95712-5
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author Beibei Chen
Huan Zhao
Huihui Hu
Haili Shang
Hui Wang
Zhentao Yao
Jinxi Huang
Huifang Lv
Weifeng Xu
Jianzheng Wang
Caiyun Nie
Jing Zhao
Yunduan He
Saiqi Wang
Xiaobing Chen
author_facet Beibei Chen
Huan Zhao
Huihui Hu
Haili Shang
Hui Wang
Zhentao Yao
Jinxi Huang
Huifang Lv
Weifeng Xu
Jianzheng Wang
Caiyun Nie
Jing Zhao
Yunduan He
Saiqi Wang
Xiaobing Chen
author_sort Beibei Chen
collection DOAJ
description Abstract Plasma DNA methylation SEPTIN9, Syndecan 2 (SDC2), and Branched Chain Amino Acid Transaminase 1 (BCAT1) tests have served as valuable diagnostic, prognostic, and predictive markers for colorectal cancer (CRC). In this study, we analyzed data including 104 eligible CRC patients, 138 colorectal benign diseases, and 106 healthy subjects in our hospital from January 2019 to May 2023. This study was approved by the Medical Ethics Committee of Henan Cancer Hospital (Approval No.2018156). A real-time polymerase chain reaction-based gene panel was used to detect the methylation of SEPTIN9, SDC2, and BCAT1. The composite score (P) was calculated according to the cycle threshold (Ct) values of the three methylated genes using the logistic regression equation. The consistency of assay and pathological diagnosis were evaluated with kappa analyzed by IBM SPSS Statistics. The median survival time was obtained by Kaplan-Meier survival analysis. Statistical figures were all carried out using Origin software. The three genes were found to be significantly methylated in ctDNA of CRC patients compared to patients with colorectal benign diseases and healthy controls. The sensitivity was 86.1%, the specificity was 97.6%, and the area under the curve of 0.929. Positive predictive value (PPV) was 57.2%, and Negative predictive value (NPV) was 99.5%. No statistically significant differences in diagnostic efficiency were observed in relation to different types of stages. Moreover, there was a significant difference in the expression of composite scores between survival periods greater than 1 year and less than 1 year (p < 0.01). The composite score (P) derived from the ctDNA methylation levels of SEPTIN9, SDC2, and BCAT1 can be used for CRC diagnosis with high sensitivity and specificity. A combination of ctDNA methylation was proved to be an effective diagnostic, prognostic, and predictive biomarker in colorectal cancer.
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spelling doaj-art-38914fcb93cc4a0b88437880c19d1f242025-08-20T02:17:47ZengNature PortfolioScientific Reports2045-23222025-04-0115111310.1038/s41598-025-95712-5Circulating DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancerBeibei Chen0Huan Zhao1Huihui Hu2Haili Shang3Hui Wang4Zhentao Yao5Jinxi Huang6Huifang Lv7Weifeng Xu8Jianzheng Wang9Caiyun Nie10Jing Zhao11Yunduan He12Saiqi Wang13Xiaobing Chen14Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Endoscopic Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Endoscopic Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalAbstract Plasma DNA methylation SEPTIN9, Syndecan 2 (SDC2), and Branched Chain Amino Acid Transaminase 1 (BCAT1) tests have served as valuable diagnostic, prognostic, and predictive markers for colorectal cancer (CRC). In this study, we analyzed data including 104 eligible CRC patients, 138 colorectal benign diseases, and 106 healthy subjects in our hospital from January 2019 to May 2023. This study was approved by the Medical Ethics Committee of Henan Cancer Hospital (Approval No.2018156). A real-time polymerase chain reaction-based gene panel was used to detect the methylation of SEPTIN9, SDC2, and BCAT1. The composite score (P) was calculated according to the cycle threshold (Ct) values of the three methylated genes using the logistic regression equation. The consistency of assay and pathological diagnosis were evaluated with kappa analyzed by IBM SPSS Statistics. The median survival time was obtained by Kaplan-Meier survival analysis. Statistical figures were all carried out using Origin software. The three genes were found to be significantly methylated in ctDNA of CRC patients compared to patients with colorectal benign diseases and healthy controls. The sensitivity was 86.1%, the specificity was 97.6%, and the area under the curve of 0.929. Positive predictive value (PPV) was 57.2%, and Negative predictive value (NPV) was 99.5%. No statistically significant differences in diagnostic efficiency were observed in relation to different types of stages. Moreover, there was a significant difference in the expression of composite scores between survival periods greater than 1 year and less than 1 year (p < 0.01). The composite score (P) derived from the ctDNA methylation levels of SEPTIN9, SDC2, and BCAT1 can be used for CRC diagnosis with high sensitivity and specificity. A combination of ctDNA methylation was proved to be an effective diagnostic, prognostic, and predictive biomarker in colorectal cancer.https://doi.org/10.1038/s41598-025-95712-5Circulating tumor DNADNA methylationColorectal cancerBiomarker
spellingShingle Beibei Chen
Huan Zhao
Huihui Hu
Haili Shang
Hui Wang
Zhentao Yao
Jinxi Huang
Huifang Lv
Weifeng Xu
Jianzheng Wang
Caiyun Nie
Jing Zhao
Yunduan He
Saiqi Wang
Xiaobing Chen
Circulating DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer
Scientific Reports
Circulating tumor DNA
DNA methylation
Colorectal cancer
Biomarker
title Circulating DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer
title_full Circulating DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer
title_fullStr Circulating DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer
title_full_unstemmed Circulating DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer
title_short Circulating DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer
title_sort circulating dna methylation based diagnostic prognostic and predictive biomarkers in colorectal cancer
topic Circulating tumor DNA
DNA methylation
Colorectal cancer
Biomarker
url https://doi.org/10.1038/s41598-025-95712-5
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