Abstract Among all the racial/ethnic groups, African American (AA) patients have the highest incidence of CRC and mortality rate. There is growing evidence indicating that the oral bacteria might translocate to the intestine, potentially causing disruptions in the balance of gut microbes. Our study delves into the complex interplay between oral pathogens, gut microbiota, and colon carcinogenesis in AA patients. Methods: 16S rRNA sequencing of tumor and non-tumor tissues, utilized qPCR for detection of oral bacteria Fusobacterium nucleatum (Fn) and Porphyromonas gingivalis (Pg) relative abundance, performed cytokine profiling via multiplex ELISA, and employed NAPPA for antibody response assessment. Results: Colon tumor tissues had lower microbial diversity, notably in right-sided tumors, with distinct biofilm-associated bacteria. Novel discoveries emerged from differential abundance testing, revealing Prevotella intermedia and Treponema socranski to be associated with early cancer stage and left-sided location, and Fusobacterium necrophorum with advanced cancer stage and right-sided location. qPCR demonstrated Fn and Pg elevation in right-sided tumors and late cancer stages. Both were detected in 45% of tumors versus 37% in non-tumor tissues and 19.15% of tumors and 25.53% in non-tumor tissues, respectively. Fn-positive groups exhibited distinct microbial signatures, with altered bacterial abundances and dysbiosis, including increased CRC-associated bacteria Faecalibacterium and Helicobacter, increased oral pathogen abundance (Fusobacterium, Porphyromonas, Prevotella, Treponema), and reduced beneficial bacteria. Serological analysis highlighted elevated levels of IL-2, IL-10, IFN-γ, and RANK in advanced cancer stages and increased CRP levels in right-sided tumors. By NAPPA analysis, 30 bacterial proteins (anti-IgG) showed a seroprevalence of more than 15% in the samples, with those being the most seroprevalent anti-HP131 and anti-HP-1564 (68% and 61% of all samples) of Helicobacter pylori, and anti-msnK (64%) of Streptococcus gallolyticus. Conclusions: Our study emphasized the reduced diversity in tumor tissues, particularly in right-sided tumors in AA colon cancer. Fn presence in colonic tumors correlated with CRC-associated bacteria and oral pathogen aggregation, suggesting its potential role in cancer pathogenesis. Combining the analysis of cytokines and pathogenic bacteria antibodies may serve as broader serological biomarkers for disease severity and location. These findings advance our comprehension of microbiota-cancer interactions, directing personalized diagnostics and treatments in this population. Citation Format: Sofia Carolina Tortora, Emily Vogtmann, Laura Martello-Rooney. Microbial signatures and serum markers in colon cancer of African American patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6696.
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