Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer

Jin-Yu Shi ^1,2, Xin Che ^2,3, Rui Wen ⁴

⁰Department of Breast Surgery, The Fifth Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China.

World Journal of Clinical Oncology +

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April 5, 2024

View abstract on PubMed

Summary

This study identifies a four-gene ferroptosis model to predict prognosis in HER2+ breast cancer (BC). Combining this model with tumor mutation burden (TMB) refines patient risk stratification for improved outcomes.

Area Of Science

Oncology
Genetics
Biomarker Discovery

Background

Ferroptosis, a form of regulated cell death, is implicated in degenerative diseases and cancer therapy.
The prognostic significance of iron metabolism-related genes in HER2-positive breast cancer (BC) remains largely unexplored.

Purpose Of The Study

To identify and validate novel ferroptosis-related biomarkers for predicting prognosis in HER2-positive breast cancer patients.
To develop a predictive model for patient stratification and therapeutic guidance.

Main Methods

Utilized TCGA and METABRIC datasets for mRNA expression and clinical data of HER2+ BC patients.
Developed and validated a four-gene (PROM2, SLC7A11, FANCD2, FH) risk prediction model.
Analyzed immune infiltration, mutation profiles, drug sensitivity, and single-cell RNA sequencing (scRNA-seq) data in relation to risk groups and tumor mutation burden (TMB).

Main Results

A higher risk score derived from the four-gene model correlated with poorer overall survival (OS) in HER2+ BC patients (P < 0.05).
Distinct patterns of immune cell infiltration, mutation, and drug sensitivity were observed between high-risk and low-risk groups.
Combining the risk score with TMB stratified patients into three distinct prognostic groups, with the highest risk and highest TMB group exhibiting the worst prognosis (P < 0.0001).
scRNA-seq revealed significant differential expression of PROM2, SLC7A11, and FANCD2 in cancer epithelial cells.

Conclusions

The developed four-gene ferroptosis model serves as an independent predictor of prognosis for HER2-positive breast cancer.
Integrating this risk model with TMB offers a more precise method for assessing patient prognosis and informs potential therapeutic strategies.

Keywords:

Ferroptosis HER2+ breast cancer Prognosis Single-cell RNA sequencing Tumor mutation burden