Pan-cancer analysis reveals netrin-1 receptors as potential tumor biomarkers and immune-related therapeutic targets

The signal pathways mediated by axon guiding molecule netrin-1 (NTN1) are transduced via its several membrane-bound receptors that include deleted in colorectal cancer (DCC), UNC5 (A-D), neogenin 1 (Neo1), melanoma cell adhesion molecule (MCAM), and Down syndrome cell adhesion molecule (DSCAM). Most of these genes play a role in the occurrence and progression of some solid tumors. Sufficient systematic studies have not been performed on the expression characteristics of the role of NTN1 and its receptors in the context of pan-cancer. Based on data from 10,437 subjects with 33 types of solid tumors in The Cancer Genome Atlas, we systematically analyzed the tumor molecular biological characteristics of NTN1 and its receptors through bioinformatics. Candidate small-molecule drugs were identified based on molecular docking analysis. Netrin-1 and its receptors exhibited stereotypical genetic alterations in tumor-suppressor genes or oncogenes. Promoter methylation and miRNA-mediated post-transcriptional inhibition likely represent the primary regulatory mechanisms, whereas the promotion of epithelial-mesenchymal transition (EMT) emerges as a conserved cellular function. we predicted potential small-molecule drugs that could bind to Netrin1 receptors. NTN1 and its receptors can be used as potential targets for tumor immunotherapy. Our results showed the important cancer biological functions of NTN1 and its receptors and their transformational value as candidate tumor biomarkers. This study also showed some critical potential immune-related therapeutic targets and provided a basis for future studies on their role in clinical immunotherapy.