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

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.

Automated summary

Based on the analysis of TNBC samples, we identified two subtypes (A and B) related to oxidative stress, with subtype A showing better prognosis. Subtype A exhibited higher immune infiltration characteristics, with tumor-suppressive immune cells, HLA genes, and three immune inhibitors being more prevalent. We also developed an eight-gene signature as an independent risk factor for TNBC and validated its predictive value. Our study reveals distinct molecular clusters based on OS-related genes, providing insights into the ROS-mediated progression and crosstalk with the tumor microenvironment in TNBC, and offering a risk prognostic model for clinical treatment decisions.