Frontiers in immunology · 2026
Integrated transcriptomic profiling reveals immune and molecular stage-specific signatures of colorectal cancer in hispanics living in Puerto Rico.
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Zenón-Meléndez Camille N, López-Acevedo Sheila N, Pérez-Santiago Josué, Ortíz-Maldonado Yakshi N, Centeno-Girona Hilmaris, Caraballo-Rivera Elba V
Аннотация
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.
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.