Plasma methylated septin 9: a colorectal cancer screening marker

Abstract

Colorectal cancer (CRC) is a slow-developing cancer (10–15 years) with one of the highest frequencies in the world’s population. Many countries have implemented various CRC screening programs, but have not achieved the desired compliance. Colonoscopy – considered the gold standard for CRC screening – has its limitations as well as the other techniques used, such as irrigoscopy, sigmoidoscopy, fecal blood and hemoglobin tests. The biomarker septin 9 has been found to be hypermethylated in nearly 100% of tissue neoplasia specimens and detected in circulating DNA fractions of CRC patients. A commercially available assay for septin 9 has been developed with moderate sensitivity (∼70%) and specificity (∼90%) and a second generation assay, Epi proColon 2.0 (Epigenomics AG), shows increased sensitivity (∼92%). The performance of the assay proved to be independent of tumor site and reaches a high sensitivity of 77%, even in early cancer stages (I and II). Furthermore, septin 9 was recently used in follow-up studies for detection of early recurrence of CRC. This article evaluates the opportunities, known limitations and future perspectives of the recently introduced Epi proColon^® 2.0 test, which is based on the detection of aberrantly methylated DNA of the v2 region of the septin 9 gene in plasma.

Keywords:

• colorectal cancer
• epigenetics
• methylation
• peripheral blood
• screening
• septin 9

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Colorectal cancer (CRC) screening currently lacks noninvasive, automated, low-cost, high sensitivity and specificity molecular methods.

• Epigenetic analysis of CRC has identified new biomarkers based on DNA methylation.

• Changes in DNA methylation can occur early in oncogenesis and detectable in plasma.

• The Epi proColon test is a CE marked IVD intended to screen for CRC in plasma utilizing methylated Septin 9.

• Further automation will bring cost reduction and enhanced availability of this blood-based CRC screening application.

Notes