Pan-Cancer Analysis Reveals Netrin-1 Receptors as Potential Tumor Biomarkers and Therapeutic Targets

Abstract

Background: The signal pathways mediated by axon guiding molecule netrin-1 (NTN1) and its receptors are deleted in colorectal cancer (DCC), Unc5A-D, Neo1, Melanoma cell adhesion molecule (MCAM), and down syndrome cell adhesion molecule (DSCAM) participate in the occurrence and progression of many tumors. Nevertheless, there has been little systematic study of the expression characteristics or the role of NTN1 and its receptors in the context of pan-cancer. Methods: Based on data from 10437 subjects in 33 types of solid tumors in The Cancer Genome Atlas, we systematically analyzed the tumor molecular biological characteristics of NTN1 and its receptors through the method of bioinformatics. Findings: We explored genetic changes in typical tumor suppressor genes or oncogenes of NTN1 and its receptors. We also elucidated the mechanisms that mediate the effects of promoter methylation and miRNA-mediated post-transcriptional inhibition on the expression of NTN1 and its receptors and the functions of NTN1 and its receptors that mediate epithelial-mesenchymal transitions. Interpretation: Our findings demonstrated critical cancer biological functions of NTN1 and its receptors and their transformational value as candidate tumor biomarkers and potential therapeutic targets. Funding: This work was supported in part by the National Natural Science Foundation of China (grant numbers 81672523, 81472404 and 81472403) and Shenyang Science and technology project (Project number 19-112-4-079). Declaration of Interests: The authors declare that no conflict of interest exists.