Fecal Bacterial Marker Noninvasively Diagnoses Colorectal Cancer

By Will Boggs MD

December 27, 2019

NEW YORK (Reuters Health) - A fecal marker of Lachnoclostridium might prove useful for noninvasively diagnosing colorectal adenoma and cancer, researchers from Hong Kong report.

Previous research suggested a role for some bacterial species, including Fusobacterium nucleatum (Fn), in promoting colorectal tumorigenesis.

In earlier studies, Dr. Jessie Qiaoyi Liang from The Chinese University of Hong Kong and colleagues identified 20 bacterial gene-marker candidates that could serve as noninvasive diagnostic biomarkers for colorectal cancer.

In the current study, they identified and evaluated the utility of a new Lachnoclostridium gene marker (which they labeled m3) for the diagnosis of colorectal adenoma and cancer. They compared diagnostic performance between this marker, other bacterial gene markers and the fecal immunochemical test (FIT) in 1,012 subjects from two independent groups.

Fecal m3 levels were significantly higher in patients with colorectal adenoma or colorectal-cancer versus controls, with a significant linear trend of m3 increasing from control to adenoma to cancer, the team reports in Gut.

At a specificity of 78.5%, m3 identified patients with adenoma with 48.3% sensitivity and 65.9% accuracy and identified patients with cancer with 62.1% sensitivity and 71.7% accuracy.

In ROC-curve analyses, Fn performed better than m3 for diagnosing colorectal cancer, whereas m3 outperformed Fn for diagnosing adenoma. Combining Fn and m3 improved the diagnostic performance for colorectal cancer but not for adenoma.

Similarly, combination with previously reported bacterial markers Fn, Bc (Bacteroides clarus), and Ch (Clostridium hathewayi) improved the diagnostic performance of m3 for colorectal cancer, but m3 alone continued to work best for adenoma.

Combination of m3 and the other three biomarkers provided higher colorectal cancer-detection rates (84.7%) than did m3 alone (61.8%) or FIT (71.3%), but the combination of all four biomarkers with FIT gave the best performance (with 93.8% sensitivity and 81.2% specificity).

m3 alone performed significantly better than FIT or all four biomarkers combined in diagnosing adenoma (with sensitivities of 48.0%, 9.3%, and 42.2%, respectively), and combination with FIT increased the sensitivity of m3 to 51.5%.

Dr. Nicholas Chia of the Mayo Clinic, in Rochester, Minnesota, who has shown that shifts in the fecal microbiota are associated with adenomatous polyps, told Reuters Health, "I think we need to have some caution with regards to these results. Other marker studies have gotten similar AUCs for adenomas of around 0.6. While 0.675 in such a large cohort is an improvement, I'm not sure it really helps very much clinically since it still means doing colonoscopies on almost everyone. It doesn't really change our approach."

"m3 appears to be an almost complete polymerase sequence," he explained. "It is difficult to say why this should be linked to adenomas or colorectal cancer. This adds some extra hesitancy in terms of being certain of the work's reproducibility, especially across cohorts."

"On the positive side, this is an important increment to our scientific knowledge," Dr. Chia said. "We would have all guessed, but did not know for certain, that additional information would lead to an improvement in our ability to identify adenomas. The identification of Lachnoclostridium as a potential target of further study is important and it is a species we have seen in our own metagenomics studies. However, there is more work that needs to be done surrounding the why."

He added that "the colorectal cancer results are already equal to what other people have found. There is not much improvement there, and not much room for improvement, in the sense that it gets harder and harder to get to 100% the closer you get to it."

The study had no commercial funding, and the researchers report no conflicts of interest.

Dr. Liang and co-author Dr. Jun Yu did not respond to a request for comments.

SOURCE: https://bit.ly/2YjN8IR Gut, online November 27, 2019.