Camille N Zenón-Meléndez, Sheila N López-Acevedo, Josué Pérez-Santiago, Yakshi N Ortíz-Maldonado, Hilmaris Centeno-Girona, Elba V Caraballo-Rivera
These findings highlight the importance of systematic DM screening, risk-stratified management, and integration of metabolic monitoring into long-term SCI care, while underscoring the need for large, prospective, and geographically diverse studies.
INTRODUCTION: Colorectal cancer (CRC) remains one of the most diagnosed malignancies worldwide and continues to rank among the leading causes of cancer-related death. Cancer progression involves dynamic transcriptional and immunological changes, and although many key molecular alterations driving CRC progression have been described, stage-specific differences remain poorly understood. This study aimed to characterize transcriptomic changes in Hispanics living in Puerto Rico (PRH) to identify relevant pathways, target genes, and stage-specific immune and molecular signatures.
METHODS: We conducted RNA sequencing (RNA-seq) from colorectal tissues, including early-stage CRC (stages I & II), advanced-stage CRC (stage III only), and adjacent mucosal tissue, to elucidate key mechanisms that modulate CRC progression.
RESULTS: Transcriptomic analysis revealed distinct gene expression patterns across stages, with a total of 1666 and 1955 differentially expressed genes at early and advanced stages, respectively. Early-stage CRC was significantly enriched for biological pathways associated with immune regulation, including cytokine signaling, epithelial barrier function, and tissue repair mechanisms, reflected in part by activation of components of the Wnt signaling pathway. In contrast, advanced-stage (stage III) CRC displayed immunosuppressive transcriptional profiles and activation of tumor-promoting pathways, including TNF signaling, enhancement of IL-17 and Wnt signaling pathways, NF-κB signaling, angiogenesis, epithelial-mesenchymal transition (EMT), and stromal remodeling.
DISCUSSION: Pathway enrichment analyses supported a shift from immune engagement and matrix remodeling in early CRC to immune evasion and pro-metastatic programs in advanced-stage disease (comprised of stage III; metastatic stage IV was not sampled). While Wnt signaling components were differentially expressed across stages, they appeared as part of a broader network of developmental and inflammatory signals driving progression. This study provides preliminary transcriptomic evidence to inform stage-specific biomarker discovery in PRH CRC that warrants further validation in larger cohorts.