Construction and validation of a necroptosis-related gene signature associated with the tumor microenvironment in melanoma

Abstract

Abstract Background Although carcinogenesis, cancer metastasis, and immunology are all closely related to necroptosis, research is still insufficient to pinpoint the precise function of necroptosis-related genes (NPRGs) in melanoma. Methods The training cohort included melanoma patient samples from The Cancer Genome Atlas (TCGA), and the validation cohort included melanoma patient samples from the Gene Expression Omnibus (GEO) database (GSE65904). The least absolute shrinkage and selection operator (LASSO) regression was used in the training cohort to construct prognostic signatures based on six NPRGs. Patients were split into groups with high and low risk. The Kaplan-Meier method compared the various risk groups' overall survival (OS). Utilizing Cox regression, the effect of their clinicopathological characteristics and risk scores on survival was assessed. The CIBERSORT method was used to evaluate the immunological microenvironment. The relationship between clinical features, levels of checkpoint gene expression, and risk scores were examined using correlation analysis. The GEPIA2 database and immunohistochemistry were used to confirm the gene expression of six NPRGs (IHC). Results The prognostic signature of the NPRGs predicted a worse OS in the high-risk group, and the test cohort corroborated this prediction. In patients with melanoma, risk scores also independently predicted survival outcomes. Significant differences existed between the various risk groups in the immune microenvironment and the expression of checkpoint genes. Necroptosis score revealed a substantial positive link with natural killer cells and M2 macrophages and a significant negative correlation with T-cell and B-cell infiltration. In the high-risk group, several immune checkpoint genes displayed low levels of expression. The results of the IHC investigation were in agreement with the expression of NPRGs from GEPIA2. Conclusion In melanoma patients, the prognostic signature linked to NPRGs can be employed as novel prognostic predictors of prognosis and the immune microenvironment.