Abstract C114: Analysis of key microbial signatures and immune response interactions in colorectal cancer cases

Abstract Colorectal cancer (CRC) ranks among the most common and lethal malignancies worldwide, accounting for 10% of all cancer cases. In Puerto Rico it is the third most prevalent cancer. In 2022, colorectal cancer ranked among the most diagnosed cancers in Puerto Rico, with a 2022 age-standardized incidence rate of 27.8 per 100,000—surpassing the U.S. rate of 27.0 per 100,000. The age-adjusted mortality rate in Puerto Rico was 13.0 per 100,000, compared to the U.S. rate of 7.9 per 100,000, highlighting a significant public health disparity. These differences may reflect variations in environmental exposures, dietary patterns, genetic susceptibility, and microbiome composition. However, role of microbial and immune factors in colorectal carcinogenesis among Puerto Rican Hispanics (PRHs) remains poorly understood. Pathogenic bacteria including Escherichia coli, Bacteroides fragilis, Fusobacterium nucleatum and Enterococcus faecalis are known to contribute to tumorigenesis through inflammation and immune modulation. Additionally, cytokines, play a critical role in CRC development by shaping the tumor microenvironment. This study aimed to characterize microbial composition, cytokine profiles, and immune signaling associated with CRC in PRHs. We analyzed plasma and tissue samples from the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR), including 15 CRC cases and 15 age- and gender-matched healthy controls. Cytokine levels were assessed using the ProcartaPlex Inflammation Panel (Luminex assay), while bacterial DNA was quantified by qPCR targeting uidA (E. coli), 16S rRNA ( B. fragilis), fus1 (F.nucleatum) and, groES (E.faecalis). Additionally, we conducted time and dose-response assays in metastatic CRC cell lines to assess the DNA damage produced by circulating bacterial DNA. Statistical analysis was performed using paired t-tests (GraphPad Prism) and ROC curve analysis using univariable and multivariable models (R studio) to evaluate diagnostic performance. CRC patients exhibited elevated plasma levels of CD62P, ICAM-1, IL-8, MCP-1, and IP-10, suggesting immune dysregulation and a tumor-promoting inflammatory milieu. Tissue levels of E. coli, F. nucleatum, and E. faecalis were significantly increased in CRC cases, supporting a role in dysbiosis and tumor progression. Among these, E. coli induced the highest DNA damage in metastatic CRC cells. A multivariable model combining MCP-1 and E.coli achieved the highest diagnostic accuracy (AUC: 0.96; 95% CI, 0.91-1.00). These findings underscore the intricate interaction between microbiota, immune signaling, and CRC development in PRHs. Population-specific research is essential for refining biomarker discovery and informing tailored prevention and diagnostic strategies that may also translate to broader U.S. populations. Citation Format: Byron K. Olivo-Natal, Sheila N. López-Acevedo, Camille N. Zenón-Meléndez, Marcia Cruz-Correa, Elba V. Caraballo-Rivera. Analysis of key microbial signatures and immune response interactions in colorectal cancer cases abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C114.