Identification and Verification of Necroptosis-Related Gene Signature and Associated Regulatory Axis in Breast Cancer

Ting Hu; Xiangwang Zhao; Yanxia Zhao; Jing Cheng; Jie Xiong; Chong Lu

doi:10.3389/fgene.2022.842218

Identification and Verification of Necroptosis-Related Gene Signature and Associated Regulatory Axis in Breast Cancer

Front Genet. 2022 Feb 16:13:842218. doi: 10.3389/fgene.2022.842218. eCollection 2022.

Authors

Ting Hu¹, Xiangwang Zhao², Yanxia Zhao¹, Jing Cheng¹, Jie Xiong¹, Chong Lu²

Affiliations

¹ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Background: Breast invasive carcinoma (BRCA) is the second leading cause of malignancy death among women. Necroptosis is a newly discovered mechanism of cell death involved in the progression and prognosis of cancer. The role of necroptosis-related genes (NRGs) in BRCA is still a mystery. Methods: LASSO Cox regression analysis was performed to construct a prognostic necroptosis-related signature. A ceRNA was constructed to explore the potential lncRNA-miRNA-mRNA regulatory axis in BRCA. Results: A total of 63 necroptosis-related genes were differentially expressed in BRCA. We also summarized the genetic mutation landscape of NRGs in BRCA. BRCA patients with low expression of BCL2 and LEF1, as well as high expression of PLK1 and BNIP3, had a poor OS, DSS, and DFS. A necroptosis-related prognostic signature with four genes (BCL2, LEF1, PLK1, and BNIP3) was constructed, and it could serve as a prognosis biomarker in BRCA, predicting the OS rate with medium to high accuracy. Moreover, the risk score was correlated with immune infiltration in BRCA. Further comprehensive analysis revealed that the expression of BCL2, LEF1, PLK1, and BNIP3 was correlated with tumor mutation burden, microsatellite instability, drug sensitivity, and pathology stage. Previous studies have been extensively studied. The roles of LEF1, PLK1, and BNIP3 in BRCA and BCL2 were selected for further analysis. We then constructed a ceRNA network, which identified an lncRNA LINC00665/miR-181c-5p/BCL2 regulatory axis for BRCA. Conclusion: The bioinformatics method was performed to develop a prognostic necroptosis-related prognostic signature containing four genes (BCL2, LEF1, PLK1, and BNIP3) in BRCA. We also constructed a ceRNA network and identified an lncRNA LINC00665/miR-181c-5p/BCL2 regulatory axis for BRCA. Further in vivo and in vitro studies should be conducted to verify these results.

Keywords: BCL2; bioinformatics analysis; breast cancer; necroptosis; prognostic biomarker.