Abstract
Background
Colorectal cancer (CRC) is a disease of global concern, and its increasing incidence suggests the need for early and accurate diagnosis. The aim of this study was to investigate the value of combined detection of SDC2, ADHFE1 and PPP2R5C gene methylation in stool samples for early CRC screening.
Methods
Stool samples from patients with CRC (n = 105), advanced adenoma (AA) (n = 54), non-advanced adenoma (NA) (n = 57), hyperplastic or other polyps (HOP) (n = 47) or no evidence of disease (NED) (n = 100) were collected from September 2021 to September 2022. The methylation levels of SDC2, ADHFE1 and PPP2R5C were quantified by quantitative methylation-specific polymerase chain reaction (qMSP), and faecal immunochemical testing (FIT) was performed. The diagnostic value was assessed using reporter operating characteristic (ROC) curve analysis.
Results
The sensitivity of combined detection of SDC2/ADHFE1/PPP2R5C methylation in predicting CRC (0–IV) was 84.8%, the specificity was 98.0%, and the AUC was 0.930 (95% CI 0.889–0.970). Compared to FIT and serum tumour biomarkers, it showed better diagnostic performance for different stages of CRC.
Conclusion
The results of this study verified that the methylation levels of SDC2, ADHFE1 and PPP2R5C in stool DNA were significantly increased in CRC patients. Combined detection of SDC2/ADHFE1/PPP2R5C methylation is a potential non-invasive diagnostic method for CRC and precancerous lesion screening.
Clinical trial registration
Chinese Clinical Trials Registry, ChiCTR2100046662, registered on 26 May 2021, prospective registration.
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Availability of data and materials
The datasets analysed in this study are available by contacting the corresponding author on reasonable request.
Abbreviations
- CRC:
-
Colorectal cancer
- AA:
-
Advanced adenoma
- NA:
-
Non-advanced adenoma
- HOP:
-
Hyperplastic or other polyps
- NED:
-
No evidence of disease
- SDC2:
-
Syndecan-2
- ADHFE1:
-
Alcohol dehydrogenase iron containing 1
- PPP2R5C:
-
Protein phosphatase 2 regulatory B, γ
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- FIT:
-
Faecal immunochemical testing
- FOBT:
-
Guaiac faecal occult blood test
- qMSP:
-
Quantitative methylation-specific polymerase chain reaction
- ROC:
-
Receiver operator characteristic curve
- AUC:
-
Area under the curve
- CI:
-
Confidence interval
- Ct:
-
Threshold cycle value
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Funding
This study was partially supported by BGI Genomics Co., Ltd. The funder had no role in the collection, analysis, or interpretation of data or in writing the manuscript.
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BL and YL designed this study and wrote the manuscript. BL and LZ contributed to stool samples and clinical information collection. YG, BL, SL and YL contributed to the experiment and data analysis. All authors helped in data interpretation and manuscript writing and reviewing and approved the final manuscript.
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This study was approved by The Affiliated Hospital of Qingdao University’s Ethics Committee (No. QYFYKYLL 965311920) and preregistered it with the Chinese Clinical Trial Registry (https://www.chictr.org.cn, Registration ID: ChiCTR2100046662). The informed consent was obtained from all subjects.
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Li, B., Liu, S., Gao, Y. et al. Combined detection of SDC2/ADHFE1/PPP2R5C methylation in stool DNA for colorectal cancer screening. J Cancer Res Clin Oncol 149, 10241–10253 (2023). https://doi.org/10.1007/s00432-023-04943-4
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DOI: https://doi.org/10.1007/s00432-023-04943-4