Research Paper Volume 12, Issue 16 pp 16457—16475
Risk stratification of cutaneous melanoma reveals carcinogen metabolism enrichment and immune inhibition in high-risk patients
- 1 Research Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P.R. China
Received: April 9, 2020 Accepted: July 7, 2020 Published: August 28, 2020https://doi.org/10.18632/aging.103734
How to Cite
Copyright © 2020 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cutaneous melanoma (CM) is the most lethal form of skin cancer. Risk assessment should facilitate stratified surveillance and guide treatment selection. Here, based on the mRNA-seq data from 419 CM patients in the Cancer Genome Atlas (TCGA), we developed a prognostic 21-gene signature to distinguish the outcomes of high- and low-risk patients, which was further validated in two external cohorts. The signature achieved a higher C-index as compared with other known biomarkers and clinical characteristics in both the TCGA and validation cohorts. Notably, in high-risk patients the expression levels of three driver genes, BRAF, NRAS, and NF1 in the MAPK pathway, were lower but exhibited a stronger positive correlation as compared with low-risk patients. Moreover, the genes involved in nicotinamide adenine dinucleotide metabolism were negatively correlated with the expression of BRAF in the high-risk group. Function analysis revealed that the upregulated genes in the high-risk group were enriched in the cytochrome P450-mediated metabolism of chemical carcinogens. Furthermore, the low-risk group had high levels of gamma delta T cells infiltration, while regulatory T cells were accumulated in the high-risk group. The present study offers a promising new prognostic signature for CM, and provides insight into the mechanisms of melanoma progression.