Comparing VIP and PD-L1 expression as cancer biomarkers

Abstract

Immune checkpoint molecules are critical targets of cancer therapies due to their ability to modulate immune responses to cancer. Vasoactive intestinal peptide (VIP) has been proposed as an immune checkpoint molecule, but its predictive and prognostic values have not been established. We evaluated expression levels of VIP and programmed death-ligand 1 (PD-L1) across different cancer types and identified specific cancer histologies in which the expression of these markers is elevated. We conducted systematic analyses of the prognostic and predictive values of VIP and PD-L1 in various cancers using publicly available patient databases and analysis tools including the Gene Expression Profiling Interactive Analysis, PrognoScan, Protein Atlas, cBioportal, and Timer2.0. We also assessed the relationship of PD-L1 and VIP expression levels with survival and the frequencies of tumor-infiltrating immune cells in various cancers. We observed a negative correlation between PD-L1 and VIP expression across cancer types, suggesting the functional redundancy of VIP and PD-L1 immunosuppressive pathways as mechanisms of immune escape. High expression levels of VIP and the association of VIP expression with immune cell infiltrates in the pancreatic adenocarcinoma tumor microenvironment suggest that VIP may be a predictive biomarker for treating pancreatic adenocarcinoma patients with drugs that inhibit the VIP signaling pathway.