Abstract 5866: Role of inflammatory cytokines and matrix metalloproteinases in colorectal cancer in a Hispanic population

Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths in Puerto Rico and the United States. Puerto Rican Hispanics (PRH) experience disproportionately higher CRC incidence and mortality rates compared to the general Hispanic population in the U.S. Biological processes, such as cytokine dysregulation and extracellular matrix remodeling, may contribute to these disparities. However, the molecular mechanisms driving CRC disease progression in PRH remain poorly understood. This study investigates the roles of inflammatory cytokines and matrix metalloproteinases (MMPs) in CRC disease progression. Methods: We conducted a case-case study using tumor (n=15) and adjacent mucosa (n=15) tissue samples collected from early (n=7) and advanced-stage (n=8) CRC archived cases recruited through the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). RNA-seq was performed and analyzed for differential gene expression and fold changes (FC) for key immune-related pathways, including MMPs, interleukin IL-17(IL17), associated cytokines, and chemokines. STRING database was used to identify protein-protein interaction networks and functional associations (≥5 gene connections). Results: Transcriptomic analysis revealed stage-specific expression patterns. IL-13 was differentially expressed in early-stage tumors, while advanced-stage tumors were characterized by CXCL10 expression Both IL-17A and IL-8 were upregulated in early and advanced stages. Elevated expression levels of IL-17A (log2 FC: 2.72 vs 3.11) and IL-8 (log2 FC: 5.73 vs 3.44) were observed in tumor tissues compared to adjacent mucosa (adj. p<0.05). Advanced-stage tumors also showed increased expression of MMP13 and MMP3, indicating extracellular matrix remodeling and invasion. IL-17A-related pathways were consistently upregulated, suggesting their involvement in chronic inflammation, tumor growth, and immune escape. Conclusions: Our results show that differential expression of IL-17A and IL-8 at early-stage CRC may contribute to immune dysregulation and a tumor-promoting microenvironment. In advanced stages, elevated MMP expression could promote extracellular matrix remodeling, metastasis, and immune evasion. These findings suggest that IL-17A, IL-8, and MMPs are potential therapeutic targets for addressing CRC disease progression and reducing health disparities among PRH. Citation Format: Elba V. Caraballo, Sheila Natalie López Acevedo, Camille Zenón-Meléndez, Josué Pérez Santiago, Marcia R. Cruz-Correa. Role of inflammatory cytokines and matrix metalloproteinases in colorectal cancer in a Hispanic population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5866.