Abstract
Recent cancer studies have found that the netrin family of proteins plays vital roles in the development of some cancers. However, the functions of the many variants of these proteins in cancer remain incompletely understood. In this work, we used the most comprehensive database available, including more than 10000 samples across more than 30 tumor types, to analyze the six members of the netrin family. We performed comprehensive analysis of genetic change and expression of the netrin genes and analyzed epigenetic and pathway relationships, as well as the correlation of expression of these proteins with drug sensitivity. Although the mutation rate of the netrin family is low in pan-cancer, among the tumor patients with netrin mutations, the highest number are Uterine Corpus Endometrial Carcinoma patients, accounting for 13.6% of cases (54 of 397). Interestingly, the highest mutation rate of a netrin family member is 38% for NTNG1 (152 of 397). Netrin proteins may participate in the development of endocrine-related tumors and sex hormone-targeting organ tumors. Additionally, the participation of NTNG1 and NTNG2 in various cancers shows their potential for use as new tumor markers and therapeutic targets. This analysis provides a broad molecular perspective of this protein family and suggests some new directions for the treatment of cancer.
Highlights
Recent cancer studies have found that the netrin family of proteins plays vital roles in the development of some cancers
Netrins associated with uterine corpus endometrial carcinoma (UCEC) exhibited the highest number of mutations (54), followed by colon adenocarcinoma (COAD) (49), skin cutaneous melanoma (SKCM) (47), stomach adenocarcinoma (STAD) (42), lung adenocarcinoma (LUAD) (38), and lung squamous cell carcinoma (LUSC) (36)
The hot spot mutation R238C/H of NTNG1 was detected in three patients with three cancers (COAD, STAD, and UCEC), and R238C was predicted as damaging in VEST3 and REVEL algorithms
Summary
Recent cancer studies have found that the netrin family of proteins plays vital roles in the development of some cancers. The participation of NTNG1 and NTNG2 in various cancers shows their potential for use as new tumor markers and therapeutic targets This analysis provides a broad molecular perspective of this protein family and suggests some new directions for the treatment of cancer. Growth factors, angiogenic factors, and extracellular proteases are secreted to the outside of the cell to produce biological functions[1] These secreted proteins participate in the immune regulation of chronic inflammation[2,3] and the occurrence of lipid metabolism diseases[4], and play important roles in tumor invasion, metastasis, immunity, and drug resistance[5,6,7,8]. We analyzed the potential cancer biological functions and common characteristics of netrin proteins in different aspects of cancer
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