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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 prevalent 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 circulating anti-F...

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Autores principales: Baik, Jung Eun, Li, Li, Shah, Manish A., Freedberg, Daniel E., Jin, Zhezhen, Wang, Timothy C., Han, Yiping W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035380/
https://www.ncbi.nlm.nih.gov/pubmed/36970057
http://dx.doi.org/10.1158/2767-9764.CRC-22-0248
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author Baik, Jung Eun
Li, Li
Shah, Manish A.
Freedberg, Daniel E.
Jin, Zhezhen
Wang, Timothy C.
Han, Yiping W.
author_facet Baik, Jung Eun
Li, Li
Shah, Manish A.
Freedberg, Daniel E.
Jin, Zhezhen
Wang, Timothy C.
Han, Yiping W.
author_sort Baik, Jung Eun
collection PubMed
description Fusobacterium nucleatum (Fn) is a gram-negative oral anaerobe and prevalent 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 circulating 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 μg/mL) compared with matched healthy controls (0.71 ± 0.36 μg/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 Medical 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 μg/mL) compared with patients with colorectal adenomas (1.49 ± 0.99 μg/mL; P = 0.025). Significant increase was limited to proximal cancers, but not distal tumors. Anti-FadAc IgG was not increased in either study population, suggesting that Fn likely translocates through the gastrointestinal 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 tumorigenesis. 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 proximal colorectal cancer. Anti-FadAc IgA may be developed into a serological biomarker for early detection of colorectal cancer.
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spelling pubmed-100353802023-03-24 Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia Baik, Jung Eun Li, Li Shah, Manish A. Freedberg, Daniel E. Jin, Zhezhen Wang, Timothy C. Han, Yiping W. Cancer Res Commun Research Article Fusobacterium nucleatum (Fn) is a gram-negative oral anaerobe and prevalent 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 circulating 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 μg/mL) compared with matched healthy controls (0.71 ± 0.36 μg/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 Medical 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 μg/mL) compared with patients with colorectal adenomas (1.49 ± 0.99 μg/mL; P = 0.025). Significant increase was limited to proximal cancers, but not distal tumors. Anti-FadAc IgG was not increased in either study population, suggesting that Fn likely translocates through the gastrointestinal 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 tumorigenesis. 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 proximal colorectal cancer. Anti-FadAc IgA may be developed into a serological biomarker for early detection of colorectal cancer. American Association for Cancer Research 2022-11-29 /pmc/articles/PMC10035380/ /pubmed/36970057 http://dx.doi.org/10.1158/2767-9764.CRC-22-0248 Text en © 2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by/4.0/This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
spellingShingle Research Article
Baik, Jung Eun
Li, Li
Shah, Manish A.
Freedberg, Daniel E.
Jin, Zhezhen
Wang, Timothy C.
Han, Yiping W.
Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia
title Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia
title_full Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia
title_fullStr Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia
title_full_unstemmed Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia
title_short Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia
title_sort circulating iga antibodies against fusobacterium nucleatum amyloid adhesin fada are a potential biomarker for colorectal neoplasia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035380/
https://www.ncbi.nlm.nih.gov/pubmed/36970057
http://dx.doi.org/10.1158/2767-9764.CRC-22-0248
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