Establishment of a prognostic model for melanoma based on necroptosis-related genes

Abstract

In this study, the clinical implications and potential functions of necroptosis-related genes (NRGs) in melanoma were systematically characterized. A novel NRG signature was then constructed to analyze the immune status and prognosis of patients with melanoma. The NRG signatures for melanoma prognosis were searched using the Cancer Genome Atlas (TCGA) dataset and followed by stepwise Cox regression analysis. Patients with melanoma were divided into two groups, and survival analysis, receiver operating characteristic (ROC), and univariate and multivariate analyses were subsequently performed. The correlation of risk score (RS) with tumor immunity and RT-polymerase chain reaction (PCR) was analyzed to further verify the gene signatures. Data on tumor mutational burden (TMB) and chromosomal copy number variation (CNV) were analyzed. Three NRGs were identified as prognostic risk signatures and were significantly related to overall survival (OS) in melanoma. The signatures had better diagnostic accuracy. Furthermore, analysis of mutations in the NRGs and the incidence of chromosomal CNV helped to reveal the relationship between mutations and melanoma occurrence. A nomogram was established based on RSs. The risk characteristics were significantly associated with immunity and high risk is closely correlated with melanoma development. In vitro experiments revealed that necrostatin-1 (Nec-1) promoted cell viability and repressed the expression levels of interleukin (IL)12A and proprotein convertase subtilisin/kexin type (PCSK)1. Additionally, the expression levels of IL12A, CXCL10, and PCSK1 decreased in tumor tissues of melanoma patients. NRGs exert vital roles in immunity and might be applied as a prognostic factor of melanoma.

Keywords: Melanoma; Necroptosis; Prognosis; Risk; Survival.