AUTHOR=Xu Yuhao , Zheng Qinghui , Zhou Tao , Ye Buyun , Xu Qiuran , Meng Xuli TITLE=Necroptosis-Related LncRNAs Signature and Subtypes for Predicting Prognosis and Revealing the Immune Microenvironment in Breast Cancer JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.887318 DOI=10.3389/fonc.2022.887318 ISSN=2234-943X ABSTRACT=Purpose

Necroptosis is a mode of programmed cell death that overcomes apoptotic resistance. We aimed to construct a steady necroptosis-related signature and identify subtypes for prognostic and immunotherapy sensitivity prediction.

Methods

Necroptosis-related prognostic lncRNAs were selected by co-expression analysis, and were used to construct a linear stepwise regression model via univariate and multivariate Cox regression, along with least absolute shrinkage and selection operator (LASSO). Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to measure the gene expression levels of lncRNAs included in the model. Based on the riskScore calculated, we separated patients into high- and low-risk groups. Afterwards, we performed CIBERSORT and the single-sample gene set enrichment analysis (ssGSEA) method to explore immune infiltration status. Furthermore, we investigated the relationships between the signature and immune landscape, genomic integrity, clinical characteristics, drug sensitivity, and immunotherapy efficacy.

Results

We constructed a robust necroptosis-related 22-lncRNA model, serving as an independent prognostic factor for breast cancer (BRCA). The low-risk group seemed to be the immune-activated type. Meanwhile, it showed that the higher the tumor mutation burden (TMB), the higher the riskScore. PD-L1-CTLA4 combined immunotherapy seemed to be a promising treatment strategy. Lastly, patients were assigned to 4 clusters to better discern the heterogeneity among patients.

Conclusions

The necroptosis-related lncRNA signature and molecular clusters indicated superior predictive performance in prognosis and the immune microenvironment, which may also provide guidance to drug regimens for immunotherapy and provide novel insights into precision medicine.