https://www.gastrojournal.org/article/S0016-5085(15)01005-7/pdf

Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers

ACG Clinical Guidelines: Colorectal Cancer Screening 2021

Epi proColon® 2.0 CE is a blood-based test designed to aid in the early detection of colorectal cancer. The test comprises a qualitative assay for the polymerase chain reaction (PCR) detection of methylated Septin9 DNA, the presence of which is associated with colorectal cancer: however, positive results should be verified by colonoscopy or sigmoidoscopy. Epi proColon® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with high clinical sensitivity and specificity in pivotal case-control studies. The sensitivity of the test did not appear to be affected by the tumour location or by patient age or gender. In addition, limited data suggest that Epi proColon® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with higher sensitivity and generally similar specificity to that of the faecal immunochemical test, and with higher sensitivity and specificity to that of the guaiac-based faecal occult blood test (statistical data not available). In an observational study, most patients who refused colonoscopy for screening accepted a non-invasive test option as an alternative, and preferred Epi proColon® 2.0 CE over a stool-based test. Large prospective trials of Epi proColon® 2.0 CE in a screening setting will be required to further elucidate the cost-effectiveness of the test. Nevertheless, currently available data suggests that Epi proColon® 2.0 CE has the potential to be a sensitive and convenient screening option for patients refusing screening by colonoscopy.

Epi proColon® 2.0 CE: A Blood-Based Screening Test for Colorectal Cancer.

The SEPT9 gene methylation assay is the first FDA-approved blood assay for colorectal cancer (CRC) screening. Fecal immunochemical test (FIT), FIT-DNA test and CEA assay are also in vitro diagnostic (IVD) tests used in CRC screening. This meta-analysis aims to review the SEPT9 assay performance and compare it with other IVD CRC screening tests. By searching the Ovid MEDLINE, EMBASE, CBMdisc and CJFD database, 25 out of 180 studies were identified to report the SEPT9 assay performance. 2613 CRC cases and 6030 controls were included, and sensitivity and specificity were used to evaluate its performance at various algorithms. 1/3 algorithm exhibited the best sensitivity while 2/3 and 1/1 algorithm exhibited the best balance between sensitivity and specificity. The performance of the blood SEPT9 assay is superior to that of the serum protein markers and the FIT test in symptomatic population, while appeared to be less potent than FIT and FIT-DNA tests in asymptomatic population. In conclusion, 1/3 algorithm is recommended for CRC screening, and 2/3 or 1/1 algorithms are suitable for early detection for diagnostic purpose. The SEPT9 assay exhibited better performance in symptomatic population than in asymptomatic population.

/pdf/the-performance-of-the-sept9-gene-methylation-assay-and-a-59rcpsrt1m.pdf

The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis.

The liquid biopsy in the management of colorectal cancer patients: Current applications and future scenarios.

Background and Aim
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).

Methods
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.

Results
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.

Conclusions
With improved performance characteristics in detecting CRC, the second-generation SEPT9 assay could play an important role in CRC screening and early detection.

Jie Hang

Papers

Performance of a second-generation methylated SEPT9 test in detecting colorectal neoplasm.