Abstract 2202: Role of FadA secreting Fusobacterium nucleatum in initiation and progression of colorectal cancer

Abstract

Abstract Colorectal cancer (CRC) is a global disease with poor prognosis. There is an alarming increase in incidence of CRC in younger patients along with well recognized racial disparities. Recent data implicate a role of microbiome in initiation and progression of CRC. Fusobacterium nucleatum (Fn), an oral opportunistic pathogen, has emerged as one of the common pathogens associated with CRC. Fn transformation from commensal to pathogen requires expression of amyloid-like FadA adhesin that plays a key role in its attachment to the colonic mucosal cells resulting in inflammatory, oncogenic, and metastatic changes. CRC initiates as polyps that go on to invade the mucosal layers and metastasize. This study analyzed the significance of Fn as a biomarker in CRC as well as to understand the etiology and metastasis of CRC. Deidentified and delinked formalin fixed paraffin embedded tissue sections from cancerous, precancerous and non-cancerous colorectal biopsies were analyzed for Fn presence and markers in epithelial to mesenchymal transition (EMT) in CRC through immunofluorescence. EMT was studied through biomarkers such as E-cadherin, which is an epithelial cell surface protein, vimentin as an intracellular filament protein normally expressed in mesenchymal cells, and N-cadherin, a cell adhesion molecule that is shown to express aberrantly in some solid tumor cells undergoing EMT. As expected, E-cadherin was abundantly expressed on the surface of epithelial cells while vimentin was found in the stromal cells in the non-cancerous tissue sections. Interestingly, the E-cadherin expression was lower in the cancerous tissue and some cancerous specimens also exhibited the vimentin positive foci within epithelial cells signifying partial EMT. N-cadherin expression was not observed in any of the specimens. The presence of Fn as analyzed through the FadA staining correlated with decline in the E-cadherin expression in some cancer specimens. To further analyze the significance of Fn, a meta-analytic study was conducted from 20 studies that indicated a significant presence of Fn not only in CRC tissues but also in fecal specimens from patients with CRC. A whole genome sequencing analysis corroborated with the abundance of Fn in CRC tissue specimens. These data suggest that analysis for Fn presence offers an attractive opportunity for intervention and targeted treatment for chemo resistant tumors. EMT analysis provides an additional corroboration in early detection of cancer progression which is pivotal in successful treatment of CRC. Citation Format: Angela Huang, Anjana Saxena, Mintoo Patel. Role of FadA secreting Fusobacterium nucleatum in initiation and progression of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2202.