期刊
AMERICAN JOURNAL OF CANCER RESEARCH
卷 12, 期 7, 页码 3128-+出版社
E-CENTURY PUBLISHING CORP
关键词
DNA methylation; epigenetic biomarker; CRC; early diagnosis; liquid biopsy
类别
资金
- Haiyan Research Fund of Harbin Medical University Cancer Hospital [JJZD2021- 05]
- Research Fund of Beijing Medical Award Foundation [YXJL-2020-1223-0320]
- Scientific Research Fund of Heilongjiang Health Commission(2020-069)
- Guangdong Basic and Applied Basic Research Foundation [2021- A1515110238]
A minimally invasive blood-based test for the detection of precancerous lesions and early-stage CRC has been developed with high accuracy. The proposed 3-gene methylation signature shows superior performance and has the potential for clinical application.
The accurate detection of colorectal cancer (CRC) at its initial stage can reduce mortality. However, the broad application of endoscopy has been limited due to the invasive procedure and patient noncompliance. Liquid biopsy with subsequent mapping of methylation in specific cell-free DNA (cfDNA) may represent an alternative approach for early diagnosis. In this study, we have developed a minimal-invasive blood-based test for detection of precancerous lesions and early-stage CRC. Using TCGA M450K methylation data, we identified candidate methylation sites with the highest Fold Change (FC) for three genes (SEPTIN9, SDC2 and VIM), which were selected from previous studies. Based on logistic regression models, we developed a 3-gene methylation signature for CRC diagnosis with high accuracy (Sensitivity =0.959, Specificity =1, AUC =0.997). Using independent public databases and data from blood samples, this model has demonstrated superior performance. The AUC was 0.919-1 and 0.905-0.916 in public tissue database for CRC and blood sample data, respectively. Thus, our proposed 3-gene methylation signature has a more reliable performance than other methods. Furthermore, signal enhancement effect of 3-gene methylation signature can improve the accuracy of early diagnosis for CRC, which demonstrates the potential for clinical application.
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