Research Paper Volume 12, Issue 20 pp 20684—20701

Comprehensive analysis of cancer hallmarks in cutaneous melanoma and identification of a novel unfolded protein response as a prognostic signature

Qi Wan1, , Lin Jin1, , Zhichong Wang1, ,

  • 1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510064, China

Received: May 27, 2020       Accepted: August 8, 2020       Published: October 26, 2020
How to Cite

Copyright: © 2020 Wan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Molecular pathways regulating the initiation and development of melanoma are potential therapeutic targets for this aggressive skin cancer. Therefore, transcriptome profiles of cutaneous melanoma were obtained from a public database and used to systematically evaluate cancer hallmark pathways enriched in melanoma. Finally, the unfolded protein response pathway was screened out, and the unfolded protein response-related genes were used to develop a robust biomarker that can predict the prognosis of melanoma, especially for younger, metastatic and high Clark level patients. This biomarker was further validated in two other independent datasets. In addition, melanoma patients were divided into high- and low-risk subgroups by applying a risk score system. The high-risk group exhibited higher immune infiltration and higher expression of N6-methyladenosine RNA methylation regulators, and had significantly shorter survival times than the low-risk subgroup. Gene Set Enrichment Analysis revealed that, among the enriched genes, gene sets involved in immune response and the extracellular matrix receptor interaction were significantly activated in the high-risk group. Our findings thus provide a new clinical application for prognostic prediction as well as potential targets for treatment of melanoma.


UPR: unfolded protein response; UPRRGs: unfolded protein response related genes; GSEA: Gene Set Enrichment Analysis; GEO: Gene Expression Omnibus; TCGA: The cancer genome atlas project; ROC: Receiver operating characteristic curve; AUC: Area under the curve; OS: Overall survival; BP: Biology process; CC: Cellular component; MF: Molecular function; KEGG: Kyoto Encyclopedia of Genes and Genomes.