Predicting the Clinical Outcome of Triple-Negative Breast Cancer Based on the Gene Expression Characteristics of Necroptosis and Different Molecular Subtypes

Abstract

Necroptosis, a kind of programmed necrotic cell apoptosis, is the gatekeeper for the host to defend against the invasion of pathogens. It helps to regulate different biological processes regarding human cancer. Nevertheless, studies that determine the impact of death on triple-negative breast cancer (TNBC) are scarce. Therefore, this paper has comprehensively examined the expression as well as clinical significance of necroptosis in TNBC. ConsensusClusterPlus was used to establish a stable molecular classification that used the expression regarding the necroptosis-linked genes. The clinical and immune characteristics of different subclasses were evaluated. Then, the weighted gene coexpression network analysis (WGCNA) assisted in determining key modules, and we selected the genes exhibiting obvious association with necroptosis prognosis through the relationship with prognosis. The univariate Cox regression analysis together with least absolute shrinkage and selection operator (LASSO) techniques served for the construction of the necroptosis-related prognostic risk score (NPRS) model, and the pathway characteristics of NPRS model grouping were further studied. Finally, the NPRS, taking into account the clinicopathological features, used the decision tree model for enhancing the prognostic model as well as the survival prediction. First, two stable molecular subtypes with different prognosis and immune characteristics were identified using necroptosis marker genes. Then, the key modules were identified, and 10 genes significantly related to the prognosis of necroptosis were selected. Then, the clinical prognostic model of NPRS was developed considering the prognosis-linked necroptosis genes. Finally, the NPRS model, taking into account the clinicopathological features, adopted the decision tree model for enhancing the prognostic model as well as the survival prediction. Herein, two new molecular subgroups considering necroptosis-linked genes are proposed, and an NPRS model composed of 10 genes is developed, which maybe assist in the personalized treatment and clinical treatment guidance of TNBC patients.