4.6 Article

Risk stratification of cutaneous melanoma reveals carcinogen metabolism enrichment and immune inhibition in high-risk patients

期刊

AGING-US
卷 12, 期 16, 页码 16457-16475

出版社

IMPACT JOURNALS LLC
DOI: 10.18632/aging.103734

关键词

cutaneous melanoma; biomarker; driver gene; metabolism; immune cell type

资金

  1. National Natural Science Foundation of China [31501065]
  2. Shenzhen Science and Technology Innovation Project [JSGG20170823 144843046]

向作者/读者索取更多资源

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.

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