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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer
Jin-Yu Shi, Xin Che, Rui Wen, Si-Jia Hou, Yu-Jia Xi, Yi-Qian Feng, Ling-Xiao Wang, Shi-Jia Liu, Wen-Hao Lv, Ya-Fen Zhang
Jin-Yu Shi, Shi-Jia Liu, Wen-Hao Lv, Ya-Fen Zhang, Department of Breast Surgery, The Fifth Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
Jin-Yu Shi, Xin Che, Ling-Xiao Wang, Shi-Jia Liu, Wen-Hao Lv, The Fifth Clinical Medical College, Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
Xin Che, Ling-Xiao Wang, Department of Colorectal Surgery, The Fifth Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
Rui Wen, College of Pharmacy, Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
Si-Jia Hou, Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
Yu-Jia Xi, Department of Urology, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
Yi-Qian Feng, Department of Breast Surgery, The First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
Author contributions: All authors participated in the conception and design of the study; conceptualization: Shi JY, Zhang YF, Wang LX; Methodology: Wen R, Shi JY, Formal analysis and investigation: Wen R, Hou SJ, Shi JY, and Che X; Writing - original draft preparation: Feng YQ and Xi YJ; Writing - review and editing: Liu SJ and Lv WH; Funding acquisition: Zhang YF; Resources: Zhang YF; Supervision: Zhang YF and Wang LX; All authors read and approved the paper.
Supported by The Science and Technology Commission of Shanxi province, No. 201901D111428.
Institutional review board statement: The study was reviewed and approved by the Shanxi Provincial People's Hospital Institutional Review Board, Approval No. 2022-240.
Informed consent statement: All study participants or their legal guardians provided informed written consent before enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ya-Fen Zhang, MD, Chief Doctor, Department of Breast Surgery, The Fifth Hospital of Shanxi Medical University, Shuangta West Street, Yingze District, Taiyuan 030000, Shanxi Province, China. cocoren2005@163.com
Received: October 17, 2023
Peer-review started: October 17, 2023
First decision: December 31, 2023
Revised: January 14, 2024
Accepted: February 3, 2024
Article in press: February 3, 2024
Published online: March 24, 2024
BACKGROUND
Ferroptosis has recently been associated with multiple degenerative diseases. Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases. However, the association of iron proliferation-related genes with prognosis in HER2+ breast cancer (BC) patients is unclear.
AIM
To identify and evaluate fresh ferroptosis-related biomarkers for HER2+ BC.
METHODS
First, we obtained the mRNA expression profiles and clinical information of HER2+ BC patients from the TCGA and METABRIC public databases. A four-gene prediction model comprising PROM2, SLC7A11, FANCD2, and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort. Patients were stratified into high-risk and low-risk groups based on their median risk score, an independent predictor of overall survival (OS). Based on these findings, immune infiltration, mutations, and medication sensitivity were analyzed in various risk groupings. Additionally, we assessed patient prognosis by combining the tumor mutation burden (TMB) with risk score. Finally, we evaluated the expression of critical genes by analyzing single-cell RNA sequencing (scRNA-seq) data from malignant vs normal epithelial cells.
RESULTS
We found that the higher the risk score was, the worse the prognosis was (P < 0.05). We also found that the immune cell infiltration, mutation, and drug sensitivity were different between the different risk groups. The high-risk subgroup was associated with lower immune scores and high TMB. Moreover, we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses. HRisk-HTMB patients had the worst prognosis, whereas LRisk-LTMB patients had the best prognosis (P < 0.0001). Analysis of the scRNA-seq data showed that PROM2, SLC7A11, and FANCD2 were significantly differentially expressed, whereas FH was not, suggesting that these genes are expressed mainly in cancer epithelial cells (P < 0.01).
CONCLUSION
Our model helps guide the prognosis of HER2+ breast cancer patients, and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.
Core Tip: A prognostic model constructed with four ferroptosis-related genes (PROM2, SLC7A11, FANCD2, and FH) combined with tumor mutation burden can be used to evaluate the prognosis of patients with HER2-positive breast cancer more accurately.
