Abstract 3274: Stage-specific deregulation of the Wnt signaling pathway in colorectal cancer among Puerto Rican Hispanics

Abstract Background: Colorectal cancer (CRC) is a significant global public health concern. It remains one of the leading causes of cancer-related deaths among Puerto Rican Hispanics (PRH), with 60-70% of cases diagnosed at advanced stages (III/IV). This highlights the urgent need for novel diagnostic biomarkers for early-stage CRC detection while monitoring those in advanced stages, which is crucial for understanding progression and guiding therapy. The Wnt signaling pathway plays a vital role in cell proliferation, differentiation, apoptosis, and cancer progression. This study aims to identify stage-specific biomarkers linked to the Wnt signaling pathway and the molecular mechanisms associated with CRC disease progression. Methods: A retrospective case-case study was conducted on 30 tissue samples from PRH recruited through the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). Transcriptomic analysis was performed in tissue samples from early (n=7) and advanced CRC stages (n=8) compared to their respective adjacent mucosal tissue as controls (adjusted p-value < 0.05). We used R statistical software (package DESeq2) for gene expression analysis between groups stratified by CRC tumor stage. Protein-protein interaction networks were generated using the STRING database to explore functional associations. Specific Wnt signaling markers, target genes, and molecular processes associated with each CRC stage will be validated using Quantinova PCR. Results: Functional interaction networks analysis (≥ 5 genes) revealed 10 Wnt signaling-associated genes uniquely deregulated in early-stage CRC and 10 in advanced-stage CRC. Differentially expressed genes in early stages included WNT1, DKK1, and DKK2, while WNT3 was exclusive to advanced stages. Additional Wnt-related genes, such as WNT2, WNT7B, and WNT5, were differentially expressed in both early and advanced stages. These findings highlight distinct patterns of Wnt signaling pathway involvement across CRC stages. Conclusion: Differential gene expression analysis of early and advanced CRC stages revealed significant deregulation of Wnt signaling pathway genes, emphasizing their potential as stage-specific diagnostic biomarkers and therapeutic targets. Future studies will focus on the modulation of these genes to study the expression and molecular mechanisms that can contribute to CRC disease progression. Understanding these molecular mechanisms is of utmost importance, as it will facilitate the development of more effective, targeted strategies for CRC diagnosis and treatment, improving outcomes for at-risk populations particularly PRH. Citation Format: Elba V. Caraballo, Camille Zenón-Meléndez, Josué Pérez-Santiago, Sheila López-Acevedo, Marcia R. Cruz-Correa. Stage-specific deregulation of the Wnt signaling pathway in colorectal cancer among Puerto Rican Hispanics [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 3274.