Oxidative stress genes define two subtypes of triple-negative breast cancer with prognostic and therapeutic implications

Frontiers in Genetics

Genetics

Shenting Liu¹  He Xu²  Kai Xu²  Ying Feng²  Renfei Du³  Wenjie Shi³  Ulf D. Kahlert³  Fanshuai Meng⁴  Luz Angela Torres-de la Roche⁵ 

[1] Department of Oncology Medicine, Hainan Cancer Hospital, Haikou, Hainan, China;Department of Thyroid and Breast Surgery, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, China;Molecular and Experimental Surgery, University Clinic for General- Visceral- Vascular- and Trans-Plantation Surgery, Medical Faculty University Hospital Magdeburg, Otto-von Guericke University, Magdeburg, Germany;Translational and Trauma Surgery Laboratory, University of Ulm, Ulm, Germany;University Hospital for Gynecology, Pius-Hospital, University Medicine Oldenburg, Carl von Ossietzky University Oldenburg, Oldenburg, Germany;

关键词: triple-negative breast cancer;    oxidative stress;    molecular subtype;    tumor microenvironment;    immunotherapy;    relapse-free survival;   

DOI  :  10.3389/fgene.2023.1230911

 received in 2023-05-29, accepted in 2023-06-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Oxidative stress (OS)-related genes have been confirmed to be closely related to the prognosis of triple-negative breast cancer (TNBC) patients; despite this fact, there is still a lack of TNBC subtype strategies based on this gene guidance. Here, we aimed to explore OS-related subtypes and their prognostic value in TNBC.Methods: Data from The Cancer Genome Atlas (TCGA)-TNBC and Sequence Read Archive (SRA) (SRR8518252) databases were collected, removing batch effects using a combat method before analysis. Consensus clustering analysis identified two OS subtypes (clusters A and B), with cluster A showing a better prognosis. Immune infiltration characteristics were analyzed using ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) algorithms, revealing higher ImmuneScore and ESTIMATEscore in cluster A. Tumor-suppressive immune cells, human leukocyte antigen (HLA) genes, and three immune inhibitors were more prevalent in cluster A.Results: An eight-gene signature, derived from differentially expressed genes, was developed and validated as an independent risk factor for TNBC. A nomogram combining the risk score and clinical variables accurately predicted patient outcomes. Finally, we also validated the classification effect of subtypes using hub markers of each subtype in the test dataset.Conclusion: Our study reveals distinct molecular clusters based on OS-related genes to better clarify the reactive oxygen species (ROS)-mediated progression and the crosstalk between the ROS and tumor microenvironment (TME) in this heterogenetic disease, and construct a risk prognostic model which could provide more support for clinical treatment decisions.

【 授权许可】

Unknown   
Copyright © 2023 Liu, Xu, Feng, Kahlert, Du, Torres-de la Roche, Xu, Shi and Meng.