The diagnostic efficiency of tissue factor pathway inhibitor 2 methylation in the detection of colorectal cancer: a systematic review and meta-analysis

• Published in: Journal of gastrointestinal oncology Vol. 16; no. 3; pp. 965 - 977
• Main Authors: Wang, Xiao-Ling, Qin, Shuo, Liu, Li, Jia, Yu-Qi, Wang, Ying, Zhou, Yu-Jie, Ramos-Molina, Bruno, Valladares-Ayerbes, Manuel, Eidens, Moritz, Liu, Zhi-Zhen
• Format: Journal Article
• Language: English
• Published: China AME Publishing Company 30.06.2025
• Subjects: Original; meta-analysis; tissue factor pathway inhibitor 2 (TFPI2); Colorectal cancer (CRC); methylation
• ISSN: 2078-6891; 2219-679X
• DOI: 10.21037/jgo-2025-319

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract. Screening of high risk populations and early diagnosis of CRC are of great importance. Tissue factor pathway inhibitor 2 ( ) methylation is an important indicator for screening CRC. However, the sensitivity and specificity of methylation vary significantly across different studies, and its diagnostic performance is susceptible to the influence of detection methods and sample types. This study set out to evaluate the diagnostic value of methylation in blood and stool samples for CRC. A search strategy based on the Population, Intervention, Comparison, Outcomes and Study (PICOS) principle was employed to retrieve relevant literatures from the PubMed, Web of Science, and EMBASE databases focused on the diagnosis of CRC patients with methylation. The literature must include the following details: the types of tissue samples tested, detailed sample sizes of both control and case groups, comprehensive diagnostic parameters, and specific methodologies for methylation detection. The quality of the included articles was evaluated using the guidelines for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Deeks' funnel plot was used for the assessment of the publication bias. Data were extracted from the studies, and the random-effects model was used for the meta-analysis. In total, 14 diagnostic test accuracy studies, comprising 3,330 subjects (1,983 CRC patients and 1,347 non-CRC controls), were included in the meta-analysis. The meta-analysis demonstrated a non-significant publication bias (P=0.29). Meta-regression further identified country, detection methodology, and sample type as significant contributors to heterogeneity. The combined sensitivity and specificity of in diagnosing CRC were 0.83 [95% confidence interval (CI): 0.72-0.91] and 0.96 (95% CI: 0.93-0.97), respectively. While the combined positive likelihood ratio (PLR) was 19.2 (95% CI: 11.1-33.5), the combined negative likelihood ratio (NLR) was 0.18 (95% CI: 0.10-0.31), the diagnostic odds ratio (DOR) was 109 (95% CI: 45-261), and the area under the summary receiver operating characteristic curve (SROC) for the included studies was 0.97 (95% CI: 0.95-0.98). Our findings showed that methylation in blood and stool samples could be a potential biomarker for the detection of CRC. methylation demonstrates potential as a non-invasive screening tool and dynamic monitoring biomarker for CRC, offering a complementary or alternative approach to invasive procedures such as colonoscopy. This is particularly applicable for preliminary risk stratification in populations with low screening adherence or high-risk profiles.