Faecal bacterial gene marker a new way to screen for CRC and recurrent adenoma

A novel faecal bacterial gene marker identified through metagenomic analysis has demonstrated high sensitivity in noninvasive detection of colorectal cancer (CRC) and recurrent colorectal adenoma, and is already available for use in clinics as a screening test.

Researchers from the Chinese University of Hong Kong (CUHK) have identified a combination of four unique bacterial DNA markers, known as m3, from a Lanchnoclostridium sp. through metagenomic analysis of stool samples from 1,012 Asian individuals (CRC, n=274; adenoma, n=353; controls, n=385). Faecal m3 is found to be significantly increased in individuals with colorectal adenoma or CRC vs controls. [Gut 2020;69:1248-1257]

“Among 1,174 individuals screened as of March 2021, m3 demonstrated an area under the receiver operating characteristic curve [AUROC] of 0.9763, a sensitivity of 94 percent, and a specificity of 85 percent in CRC detection,” said Professor Jun Yu of the Department of Medicine and Therapeutics, CUHK.

According to the researchers, the sensitivity of m3 in CRC detection is comparable to that of colonoscopy. “Given its significantly higher sensitivity compared with faecal immunochemistry test [FIT] in detecting stage I–III CRC, the m3 test is suitable for use as a first-line screening test for early CRC,” Yu suggested.

“More importantly, the m3 bacterial gene marker test is the world’s only test that can detect recurrent colorectal adenoma,” said Professor Siew Ng, Associate Director of the Centre for Gut Microbiota Research, CUHK.

“In more than 200 individuals who had undergone colorectal adenoma resection within 5 years, the m3 test detected recurrent adenoma with an AUROC of 0.950, a sensitivity of 90 percent, and a specificity of 87 percent,” reported Dr Jessie Liang of the Department of Medicine and Therapeutics, CUHK. “In comparison, the sensitivity of FIT in detecting recurrent adenoma is only 8.3 percent.”

“The noninvasive m3 test can be used as a first-line screening test for colorectal adenoma and CRC every 1–3 years in individuals ≥45 years of age, and yearly in those at high risk,” said Ng. “It is complementary to other tests currently available for CRC screening.”

“The m3 test can also be used for routine surveillance of gut microbiota in individuals of any age. It informs individuals of their risks of colorectal adenoma and CRC, with dietary recommendations provided to help modify their CRC risk. This is particularly important for high-risk individuals, such as those with obesity, type 2 diabetes, a family history of CRC, a history of colorectal adenoma or CRC, or unhealthy lifestyles,” Ng continued. “It requires only a small sample of stool that can be collected at home. Results are available in 4 hours.”

“The faecal m3 test costs much less than a colonoscopy and is already available at clinics. It helps prioritize colonoscopy in high-risk individuals while sparing those at low risk from the procedure,” said Professor Francis Chan, Dean of Medicine and Director of the Centre for Gut Microbiota Research, CUHK. “With the large number of people eligible for CRC screening, we hope that the m3 test will be introduced into the government’s CRC screening programme in the future.”