Solutions for Colorectal Cancer Early Detection Linked to Oral Health

"Notes from the Lab" spotlights innovative work addressing problems in cancer research and care from Columbia investigators, post-docs, fellows, and students.

December 1, 2022
Faculty member in lab
Yiping Han, PhD, professor of microbial sciences (in Dental Medicine and Microbiology and Immunology, Obstetrics and Gynecology and Medical Sciences in Medicine); member of the Tumor Biology and Microenvironment Program at the Herbert Irving Comprehensive Cancer Center

The Han Lab

Our main research interests lie in host-pathogen interaction, with an emphasis on the oral cavity. We’ve pioneered studies in investigating how oral bacteria can impact health and disease in other parts of the body.

The Research

“Circulating IgA antibodies against the Fusobacterium nucleatum adhesin FadA are a potential biomarker for colorectal neoplasia,” published in Cancer Research Communications

The cancer problem we are solving

More than 10 years ago, we laid the research groundwork demonstrating that oral bacteria don’t remain confined in the mouth or oral cavity, but can translocate to different parts of the body. These bacteria may remain benign in the mouth but once they travel to other parts of the body, they can become pathogens. 

A type of cancer-associated bacteria, Fusobacterium nucleatum (F. nucleatum), is our lab’s main interest area. We’ve published papers on F. nucleatum and its role in colorectal cancer, the third leading cause of cancer-related deaths in men and in women in the U.S., and the second most common cause of cancer deaths. Not all colorectal or gastrointestinal cancers have these bacteria but for the ones that do, there are common features, including worse prognosis, drug resistance, and shorter survival. We’re further investigating F. nucleatum’s role in colorectal cancer, focusing on diagnosis and disease progression, and aiming to identify its clinical relevance in patients.

What we’ve uncovered so far

Using in vitro tissue culture and in vivo mouse models of colorectal cancer developed by our lab, we have identified a unique adhesin called FadA, from F. nucleatum, that plays an essential virulent role. FadA is an adhesin allowing the bacteria to attach to host cells. Interestingly, we discovered that FadA undergoes dramatic structural changes in disease conditions to become “amyloid-like”. Amyloids are best known as protein plaques found in the brains of patients with Alzheimer’s diseases. We found the amyloid-like FadA can function as a molecular switch to convert F. nucleatum from benign to pathogenic. 

In prior studies, we’ve demonstrated that F. nucleatum adheres to, invades and induces oncogenic and inflammatory responses to stimulate growth of colorectal cancer cells through its unique FadA adhesin. This work dates back 10 years ago, when F. nucleatum was first linked to colorectal cancer. We’ve been aiming since to understand whether this bacterium serves as a “passenger” or a “driver” of cancer. Does it play a causal role? And we’ve shown that it does; it directly stimulates cancer growth.

Main takeaway from the new research

We investigated antibody levels that recognize the amyloid-like FadA complex (FadAc) in colorectal cancer patients in two study populations—in early stage and advanced colorectal cancer patients compared to normal controls in one group and in colorectal cancer compared to advanced pre-cancerous polyps in another group. Interestingly, we found increased levels of circulating immunoglobulin A (IgA), antibodies primarily produced at mucosal surfaces like the respiratory and digestive tracts, in both early and advanced colorectal cancer patients compared to the healthy controls, and especially in the patients with cancers located in the colon on the right side (ascending colon), which is closest to the stomach. 

Why this is important

We think that Anti-FadAc IgA may be developed into a serological biomarker—a liquid biopsy—for early detection of colorectal cancer.

Next Steps

We’d like to expand our proof-of-concept study to a larger population. We plan to investigate further whether our FadA-based findings for colorectal cancer detection can be eventually developed into an effective diagnostic test. The advantage of developing a new liquid biopsy for colorectal cancer is that it is non-invasive and a much easier test to administer.

Our goal

To develop diagnostics and therapeutics based on what we continue to uncover and understand about the mechanisms of F. nucleatum in cancer.

References

Collaborators at Columbia University unless noted otherwise: Jung Eun Baik, Li Li (University of Virginia), Manish A. Shah (Weill Cornell), Daniel E. Freedberg, Zhezhen Jin, Timothy C. Wang