What question did this study set out to answer?

This research aims to investigate the relationships between TIGIT, CD155, gene mutations, and immune profiles in colorectal cancer.

January 22, 2026Open Access

Association of TIGIT and CD155 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, MSI Status, and Cytokine Profiles in Colorectal Cancer

Key Points

This research aims to investigate the relationships between TIGIT, CD155, gene mutations, and immune profiles in colorectal cancer.
Measured TIGIT and CD155 proteins using ELISA in CRC tumors and surgical margins.
Evaluated associations with mutations in KRAS, NRAS, BRAF, PIK3CA, and AKT1 along with MSI status.
Performed cytokine profiling and external validation using TCGA transcriptomic data.
TIGIT and CD155 levels were significantly higher in tumor tissues than surgical margins.
TIGIT was more elevated in microsatellite unstable tumors and BRAF-mutant tumors.
MSI status was associated with varying levels of TIGIT, but not with CD155; cytokine profiling linked IFN-g with both proteins.

Abstract

TIGIT and its ligand CD155 (PVR) are emerging immune checkpoints in colorectal cancer (CRC), but their associations with mutational subtypes and the tumor immune milieu remain unclear. We quantified TIGIT and CD155 proteins by ELISA in paired CRC tumors and matched surgical margins (n = 131) and evaluated associations with clinicopathological features, MSI status, and KRAS/NRAS/BRAF/PIK3CA/AKT1 mutations (n = 104). Both TIGIT and CD155 were significantly elevated in tumor tissue versus margins (p < 0.0001) and showed no association with TNM stage, clinical stage, grade, or tumor location. TIGIT levels were higher in MSI than MSS tumors and in BRAF-mutant compared to BRAF wild-type tumors, while CD155 expression showed no consistent MSI- or mutation-dependent differences. Cytokine profiling identified IFN-g as the only shared positive associate of TIGIT and CD155; CD155 additionally associated with TRAIL, IL-1Ra, M-CSF, and PDGF-bb. In external transcriptomic validation (TCGA-CRC), GSEA indicated enrichment of interferon/inflammatory programs in TIGIT-high tumors, while CD155-high tumors preferentially showed proliferation-related MYC/E2F/G2M signatures. Together, these findings support tumor-wide upregulation of the TIGIT/CD155 axis in CRC and suggest that TIGIT, more than CD155, tracks with MSI/BRAF-associated immune activation, providing a rationale for patient stratification in checkpoint-directed immunotherapy.

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