A Novel Gene Signature Based on Immunogenic Cell Death-Related Genes Predicts the Prognosis and Immune Infiltration Status of Melanoma Patients

Abstract

Background: The accumulating evidence suggests that immunogenic cell death (ICD) proves to be an effective therapeutic strategy for various tumors. This study aims to establish a model for the predictive evaluation of melanoma and investigate the potential clinical applications of ICD. Methods: The mRNA profile data of melanoma samples, sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, were employed to examine the expression patterns of genes associated with ICD in melanoma. Practical enhancement methods were applied to investigate the biological function of differentially expressed ICD-related genes. Multiple immune estimation approaches were employed to assess the infiltration of the immune landscape of samples in various clusters, aiming to explore the interaction between ICD and the immune system. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the expression levels of key genes. Results: Through unsupervised clustering analysis, melanoma patients were categorized into two distinct clusters based on the expression patterns of ICD-related genes. The overall survival rate was significantly higher in the group with elevated expression. The proportion of macrophages in the high-expression group was considerably greater. Additionally, ICD played a positive role in triggering anti-tumor immunity. Lastly, eight important candidate genes were identified to construct the prognostic model for melanoma patients. The qRT-PCR confirmed the increased level of BAX in melanoma cells, while decreased levels of ATG5, CASP8, CD8A, CXCR3, EIF2AK3, IFNG, and PIK3CA were observed. Conclusions: This research illustrates the potential role of ICDs in the prognosis and treatment of melanoma. The development of a prognostic model based on this information could offer a reliable prognostic prediction for melanoma patients, aiding in the individualization of patient treatment.