Comprehensive Analysis of Necroptosis-Related Genes as Prognostic Factors and Immunological Biomarkers in Breast Cancer

Abstract

Breast cancer (BC) is a lethal malignancy with a poor prognosis. Necroptosis is critical in the progression of cancer. However, the expression of genes involved in necroptosis in BC and their association with prognosis remain unclear. We investigated the predictive potential of necroptosis-related genes in BC samples from the TCGA dataset. We used LASSO regression to build a risk model consisting of twelve necroptosis-related genes in BC. Using the necroptosis-related risk model, we were able to successfully classify BC patients into high- and low-risk groups with significant prognostic differences (p = 4.872 × 10 −7). Additionally, we developed a matched nomogram predicting 5, 7, and 10-year overall survival in BC patients based on this necroptosis-related risk model. Our next step was to perform multiple GSEA analyses to explore the biological pathways through which these necroptosis-related risk genes influence cancer progression. For these twelve risk model genes, we analyzed CNV, SNV, OS, methylation, immune cell infiltration, and drug sensitivity in pan-cancer. In addition, immunohistochemical data from the THPA database were used to validate the protein expression of these risk model genes in BC. Taken together, we believe that necroptosis-related genes are considered potential therapeutic targets in BC and should be further investigated.

Keywords

• TCGA
• breast cancer
• necroptosis
• risk model
• GSEA