A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA
Abstract Background Methylated SDC2 has been proved as a diagnostic marker for human colorectal cancer (CRC), noninvasive stool DNA-based methylation testing also emerges as a novel approach for detecting CRC. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 met...
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| Format: | Article |
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BMC
2022-04-01
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| Series: | BMC Gastroenterology |
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| Online Access: | https://doi.org/10.1186/s12876-022-02264-3 |
| _version_ | 1818147320898781184 |
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| author | Liang Ma Geng Qin Fei Gai Yongwei Jiang Zhan Huang Hui Yang Shukun Yao Shiyu Du Yongtong Cao |
| author_facet | Liang Ma Geng Qin Fei Gai Yongwei Jiang Zhan Huang Hui Yang Shukun Yao Shiyu Du Yongtong Cao |
| author_sort | Liang Ma |
| collection | DOAJ |
| description | Abstract Background Methylated SDC2 has been proved as a diagnostic marker for human colorectal cancer (CRC), noninvasive stool DNA-based methylation testing also emerges as a novel approach for detecting CRC. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 methylation test by a new qPCR detection reagent for early detection of CRC. Methods A new qPCR detection reagent contained two differentially methylated regions in SDC2 CpG islands for the detection of CRC was used in this study. Performance of the SDC2 methylation detection reagent was evaluated by analyzing limit of detection, precision, and specificity. The effect of interfering substances on assay performance was also tested. 339 subjects (102 CRC patients, 50 patients with advanced adenomas, 39 patients with non-advanced adenomas, 18 colitis patients and 130 normal individuals) from the China-Japan Friendship Hospital were evaluated. Approximately 2.5 g of stool sample was collected from each participant. Stool DNA was extracted and bisulfite-converted, followed by qPCR assay, which contained two pairs of primers for the methylation detection of two fragments of the SDC2 gene (named SDC2-A and SDC2-B). The diagnostic value of this test in CRC was evaluated by calculating receiver operating characteristic (ROC) curve, and value of the area under the curve (AUC). Results The test kit was able to detect methylated SDC2 in stool DNA samples with concentrations as low as 90 copies/μL in 100% of replicates. The sensitivity for detecting CRC by methylated SDC2-A alone was 85.29% (95% CI 77.03–91.00%) with a specificity of 96.15% (95% CI 91.08–98.58%). The sensitivity by methylated SDC2-B alone was 83.33% (95% CI 74.82–89.42%) with a specificity of 97.69% (95% CI 93.14–99.51%). However, when methylated SDC2-A and methylated SDC2-B were combined, the sensitivity for CRC detection improved to 87.25% (95% CI 79.27–92.53%) with a specificity of 94.62% (95% CI 89.11–97.56%). Further, the detection reagent achieved ROC-AUC 0.874 (95% CI 0.822–0.927) for SDC2-A, 0.906 (95% CI 0.859–0.952) for SDC2-B, and 0.939 (95% CI 0.902–0.977) for SDC2-Combine A&B. Conclusions This study validated the capability of stool DNA-based SDC2 methylation test for early screening of CRC, and combined detection of two fragments of SDC2 gene could improve detection sensitivity. |
| first_indexed | 2024-12-11T12:33:23Z |
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| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-12-11T12:33:23Z |
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| spelling | doaj.art-2c443794e3b848f8ba6b02f6569044c42022-12-22T01:07:11ZengBMCBMC Gastroenterology1471-230X2022-04-0122111010.1186/s12876-022-02264-3A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNALiang Ma0Geng Qin1Fei Gai2Yongwei Jiang3Zhan Huang4Hui Yang5Shukun Yao6Shiyu Du7Yongtong Cao8Clinical Laboratory, China-Japan Friendship HospitalDepartment of Gastroenterology, China-Japan Friendship HospitalMedical Business Unit, Amoy Diagnostics Co. Ltd.Clinical Laboratory, China-Japan Friendship HospitalMedical Business Unit, Amoy Diagnostics Co. Ltd.Clinical Laboratory, China-Japan Friendship HospitalDepartment of Gastroenterology, China-Japan Friendship HospitalDepartment of Gastroenterology, China-Japan Friendship HospitalClinical Laboratory, China-Japan Friendship HospitalAbstract Background Methylated SDC2 has been proved as a diagnostic marker for human colorectal cancer (CRC), noninvasive stool DNA-based methylation testing also emerges as a novel approach for detecting CRC. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 methylation test by a new qPCR detection reagent for early detection of CRC. Methods A new qPCR detection reagent contained two differentially methylated regions in SDC2 CpG islands for the detection of CRC was used in this study. Performance of the SDC2 methylation detection reagent was evaluated by analyzing limit of detection, precision, and specificity. The effect of interfering substances on assay performance was also tested. 339 subjects (102 CRC patients, 50 patients with advanced adenomas, 39 patients with non-advanced adenomas, 18 colitis patients and 130 normal individuals) from the China-Japan Friendship Hospital were evaluated. Approximately 2.5 g of stool sample was collected from each participant. Stool DNA was extracted and bisulfite-converted, followed by qPCR assay, which contained two pairs of primers for the methylation detection of two fragments of the SDC2 gene (named SDC2-A and SDC2-B). The diagnostic value of this test in CRC was evaluated by calculating receiver operating characteristic (ROC) curve, and value of the area under the curve (AUC). Results The test kit was able to detect methylated SDC2 in stool DNA samples with concentrations as low as 90 copies/μL in 100% of replicates. The sensitivity for detecting CRC by methylated SDC2-A alone was 85.29% (95% CI 77.03–91.00%) with a specificity of 96.15% (95% CI 91.08–98.58%). The sensitivity by methylated SDC2-B alone was 83.33% (95% CI 74.82–89.42%) with a specificity of 97.69% (95% CI 93.14–99.51%). However, when methylated SDC2-A and methylated SDC2-B were combined, the sensitivity for CRC detection improved to 87.25% (95% CI 79.27–92.53%) with a specificity of 94.62% (95% CI 89.11–97.56%). Further, the detection reagent achieved ROC-AUC 0.874 (95% CI 0.822–0.927) for SDC2-A, 0.906 (95% CI 0.859–0.952) for SDC2-B, and 0.939 (95% CI 0.902–0.977) for SDC2-Combine A&B. Conclusions This study validated the capability of stool DNA-based SDC2 methylation test for early screening of CRC, and combined detection of two fragments of SDC2 gene could improve detection sensitivity.https://doi.org/10.1186/s12876-022-02264-3Colorectal cancerCombined detectionMethylationSDC2Stool DNA |
| spellingShingle | Liang Ma Geng Qin Fei Gai Yongwei Jiang Zhan Huang Hui Yang Shukun Yao Shiyu Du Yongtong Cao A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA BMC Gastroenterology Colorectal cancer Combined detection Methylation SDC2 Stool DNA |
| title | A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA |
| title_full | A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA |
| title_fullStr | A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA |
| title_full_unstemmed | A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA |
| title_short | A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA |
| title_sort | novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan 2 sdc2 in stool dna |
| topic | Colorectal cancer Combined detection Methylation SDC2 Stool DNA |
| url | https://doi.org/10.1186/s12876-022-02264-3 |
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