CDH17 as a Cell Surface Immunotherapy Target in Colorectal Cancer: An In Silico Analysis

Abstract

Immunotherapy development against colorectal cancer (CRC) is hindered by the lack of surface antigen highly expressed in cancer cells but with restricted presence in normal tissues to minimize off-tumor toxicities. In this in silico analysis, a longlist of genes (n=13,488) expressed in CRCs according to the Human Protein Atlas (HPA) database were evaluated to shortlist for potential surface targets based on the following prerequisites: (i) Absent from the brain and lung tissues to minimize the likelihood of neurologic and pulmonary toxicities; (ii) Restricted expression profile in other normal human tissues; (iii) Genes that potentially encode cell surface proteins and; (iv) At least moderately expressed in CRC cases. Fifteen potential targets were shortlisted and subsequently ranked according to the combination of their transcript and protein expression levels in CRCs derived from multiple datasets (i.e. DepMap, TCGA, CPTAC-2, and HPA CRCs). The top-ranked target with the highest and homogenous expression in CRCs was cadherin 17 (CDH17). Downstream in silico analyses in CRC cases showed that CDH17 was highly correlated with carcinoembryonic antigen expression, CDH17 expression was lower in cases with high microsatellite instability, as well as negatively associated with the expression of MHC class I and II molecules. In summary, CDH17 represents an optimal target for immunotherapy development against CRCs, and this study provides a framework to shortlist for promising surface targets for immunotherapy development against other malignancies.