Establishment of a Cell Necroptosis Index to Predict Prognosis and Drug Sensitivity for Patients With Triple-Negative Breast Cancer

Abstract

Background: Necroptosis has been an alternatively identified mechanism of programmed cancer cell death, which plays a significant role in cancer. However, research about necroptosis-related long noncoding RNAs (lncRNAs) in cancer are still few. Moreover, the potentially prognostic value of necroptosis-related lncRNAs and their correlation with the immune microenvironment remains unclear. The present study aimed to explore the potential prognostic value of necroptosis-related lncRNAs and their relationship to immune microenvironment in triple-negative breast cancer (TNBC).Methods: The RNA expression matrix of patients with TNBC was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Finally, 107 patients of GSE58812, 159 patients of TCGA, and 143 patients of GSE96058 were included. Necroptosis-related lncRNAs were screened by Cox regression and Pearson correlation analysis with necroptosis-related genes. By LASSO regression analysis, nine necroptosis-related lncRNAs were employed, and a cell necroptosis index (CNI) was established; then, we evaluated its prognostic value, clinical significance, pathways, immune infiltration, and chemotherapeutics efficacy.Results: Based on the CNI value, the TNBC patients were divided into high- and low-CNI groups, and the patients with high CNI had worse prognosis, more lymph node metastasis, and larger tumor (p < 0.05). The receiver operating characteristic (ROC) analysis showed that the signature performed well. The result of the infiltration proportion of different immune cell infiltration further explained that TNBC patients with high CNI had low immunogenicity, leading to poor therapeutic outcomes. Moreover, we found significant differences of the IC50 values of various chemotherapeutic drugs in the two CNI groups, which might provide a reference to make a personalized chemotherapy for them.Conclusion: The novel prognostic marker CNI could not only precisely predict the survival probability of patients with TNBC but also demonstrate a potential role in antitumor immunity and drug sensitivity.

Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma

“…In addition, Xie et al. identified the necroptosis-related long noncoding RNAs in triple-negative breast cancer, and the subgroup with high nine necroptosis-related long noncoding RNAs signature score had poor prognosis ( 25 ). In this study, we constructed a novel prognostic model based on necroptosis-associated genes KPNA2, SLC1A5, and RAMP3.…”

Comprehensive analysis of the endoplasmic reticulum stress-related long non-coding RNA in bladder cancer

“…Xie et al. ( 24 ) constructed a necroptosis signature to predict prognosis and drug sensitivity of triple-negative breast cancer. Meanwhile, a ferroptosis-based signature has been established, which may serve as a novel therapy biomarker for lung squamous cell carcinoma ( 25 ).…”

Development and validation of a novel necroptosis-related score to improve the outcomes of clear cell renal cell carcinoma

“…Currently, genetic markers associated with necroptosis have been constructed in various cancers (e.g., Hepatocellular carcinoma and breast cancer) ( Hu et al, 2022 ; Yang and Jiang, 2022 ). Additionally, Xie and others constructed a powerful necroptosis index to accurately predict prognosis in triple-negative breast cancer ( Xie et al, 2022 ). But unfortunately, these genetic markers were constructed through public datasets and lacked suitable external cohorts to conduct in-depth exploration of the validity.…”