Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia

Fusobacterium nucleatum (Fn) is a gram-negative oral anaerobe and preva-lent in colorectal cancer. Fn encodes a unique amyloid-like adhesin, FadA complex (FadAc), consisting of intact pre-FadA and cleaved mature FadA, to promote colorectal cancer tumorigenesis. We aimed to evaluate cir-culating anti-FadAc antibody levels as a biomarker for colorectal cancer. Circulating anti-FadAc IgA and IgG levels were measured by ELISA in two study populations. In study 1, plasma samples from patients with colorectal cancer (n = 25) and matched healthy controls (n = 25) were obtained from University Hospitals Cleveland Medical Center. Plasma levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (mean + SD: 1.48 + 1.07 & mu;g/mL) compared with matched healthy controls (0.71 + 0.36 & mu;g/mL; P = 0.001). The increase was significant in both early (stages I and II) and advanced (stages III and IV) colorectal cancer. In study 2, sera from patients with colorectal cancer (n = 50) and patients with advanced colorectal adenomas (n = 50) were obtained from the Weill Cornell Medi-cal Center biobank. Anti-FadAc antibody titers were stratified according to the tumor stage and location. Similar as study 1, serum levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (2.06 + 1.47 & mu;g/mL) compared with patients with colorectal adenomas (1.49 + 0.99 & mu;g/mL; P = 0.025). Significant increase was limited to proximal can-cers, but not distal tumors. Anti-FadAc IgG was not increased in either study population, suggesting that Fn likely translocates through the gas-trointestinal tract and interact with colonic mucosa. Anti-FadAc IgA, but not IgG, is a potential biomarker for early detection of colorectal neoplasia, especially for proximal tumors.Significance: Fn, an oral anaerobe highly prevalent in colorectal cancer, secretes the amyloid-like FadAc to promote colorectal cancer tumorige-nesis. We report that circulating levels of anti-FadAc IgA, but not IgG, are increased in patients with both early and advanced colorectal cancer compared with the healthy controls, and especially in those with proxi-mal colorectal cancer. Anti-FadAc IgA may be developed into a serological biomarker for early detection of colorectal cancer.