Diagnostic Performance of DNA Hypermethylation Markers in Peripheral Blood for the Detection of Colorectal Cancer: A Meta-Analysis and Systematic Review

Abstract

DNA hypermethylation in blood is becoming an attractive candidate marker for colorectal cancer (CRC) detection. To assess the diagnostic accuracy of blood hypermethylation markers for CRC in different clinical settings, we conducted a meta-analysis of published reports. Of 485 publications obtained in the initial literature search, 39 studies were included in the meta-analysis. Hypermethylation markers in peripheral blood showed a high degree of accuracy for the detection of CRC. The summary sensitivity was 0.62 [95% confidence interval (CI), 0.56–0.67] and specificity was 0.91 (95% CI, 0.89–0.93). Subgroup analysis showed significantly greater sensitivity for the methylated Septin 9 gene (SEPT9) subgroup (0.75; 95% CI, 0.67–0.81) than for the non-methylated SEPT9 subgroup (0.58; 95% CI, 0.52–0.64). Sensitivity and specificity were not affected significantly by target gene number, CRC staging, study region, or methylation analysis method. These findings show that hypermethylation markers in blood are highly sensitive and specific for CRC detection, with methylated SEPT9 being particularly robust. The diagnostic performance of hypermethylation markers, which have varied across different studies, can be improved by marker optimization. Future research should examine variation in diagnostic accuracy according to non-neoplastic factors.

Advance in plasma SEPT9 gene methylation assay for colorectal cancer early detection

“…Currently, CRC screening approaches are divided into two categories: Invasive and noninvasive methods. The invasive methods, such as colonoscopy, remain the main screening tools due to their very good diagnostic performance, enabling the detection and removal of precancerous lesions[ 5 ]. However, it requires thorough bowel preparations.…”

Epigenetics of colorectal cancer: emerging circulating diagnostic and prognostic biomarkers

“…Data from subgroup analysis showed that the pooled sensitivity was higher for studies evaluating SEPT9 methylation than for studies evaluating genes different from SEPT9 (75% vs. 58%) while the pooled specificity was almost comparable (0.89 vs. 0.91). No significant difference among other subgroups including multiple target genes vs. single target gene and qPCR based methods vs. other methods were observed (28).…”

Fecal immunochemical tests in combination with blood tests for colorectal cancer and advanced adenoma detection—systematic review

“…Studies examining diagnostic performance of blood markers for CRC detection were systematically reviewed already. 9,25,26 However, these studies did not examine their test performance when combined with FIT. Liu et al 9 waived a conclusion on which biomarker to recommend, whereas Shah et al 25 highlighted the promising results of DNA hypermethylation markers, specifically Septin9 expression and other DNA and microRNA (miRNA) panels.…”