Performance of a second‐generation methylated <scp>SEPT9</scp> test in detecting colorectal neoplasm

TLDR

Screening and early detection reduce colorectal cancer mortality, and methylated SEPT9 is a novel blood‑based biomarker for CRC. The study evaluated the performance of the second‑generation SEPT9 assay for detecting colorectal neoplasm and compared it with fecal immunochemical test (FIT). The study enrolled 135 CRC, 169 adenomatous polyps, 81 hyperplastic polyps, and 91 healthy controls, verified by colonoscopy, and performed peripheral blood SEPT9 testing with Epi proColon 2.0; in 177 patients both SEPT9 and FIT were administered. The second‑generation SEPT9 assay achieved 74.8 % sensitivity and 87.4 % specificity for CRC, detected 66.7–100 % of stages I–IV tumors, had 27.4 % sensitivity for advanced adenomas, outperformed FIT (58.0 % sensitivity, 82.4 % specificity) for CRC, and showed comparable performance for advanced adenomas, indicating its potential as a screening tool.

Abstract

Screening and early detection reduces mortality due to colorectal cancer (CRC). Methylated Septin 9 (SEPT9) is a new blood-based biomarker for CRC. We evaluated the performance of the second-generation SEPT9 assay for the detection of colorectal neoplasm, and compared it with fecal immunochemical test (FIT).A total of 135 patients with CRC, 169 with adenomatous polyps, 81 with hyperplastic polyps, and 91 healthy controls were included. The clinical status of all subjects was verified by colonoscopy. In all patients, peripheral blood samples were taken for SEPT9 testing using Epi proColon 2.0 test. For 177 patients, both SEPT9 and FIT were performed.The sensitivity and specificity of SEPT9 for CRC were 74.8% (95% confidence interval [CI]: 67.0-81.6%) and 87.4% (vs non-CRC, 95% CI: 83.5-90.6%), respectively. SEPT9 was positive in 66.7% of stage I, 82.6% of stage II, 84.1% of stage III, and 100% of stage IV CRCs. The sensitivity of SEPT9 for advanced adenomas was 27.4% (95% CI: 18.7-37.6%). The sensitivity and specificity of FIT for CRC was 58.0% (95% CI: 46.1-69.2%) and 82.4% (95% CI: 74.4-88.7%), respectively. SEPT9 showed better performance in CRC detection than FIT, but similar among advanced adenomas.With improved performance characteristics in detecting CRC, the second-generation SEPT9 assay could play an important role in CRC screening and early detection.