Comprehensive analysis of mitochondrial metabolism–associated clusters and prognostic scoring model index construction in breast cancer
5 affiliations
- 1Zhejiang University School of Medicine
- 2Institute of Translational Medicine, Zhejiang University School of Medicine
- 3Department of Breast Surgery, The First People’s Hospital of Aksu Prefecture
- 4Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
- 5Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine
Abstract
Further stratification of breast cancer (BC) prognosis is of considerable clinical importance, yet the mechanistic role of mitochondrial metabolism in BC progression remains incompletely understood. In this study, we systematically identified mitochondrial metabolism–associated genes (MMAGs) linked to BC prognosis by integrating clinical survival data and developed an MMAG-based risk scoring system using univariate and multivariate Cox regression combined with least absolute shrinkage and selection operator (LASSO) analysis. We characterized the relationship between MMAG-defined clusters, immune microenvironment infiltration, and clinicopathological features, and employed single-cell RNA sequencing to delineate MMAG expression patterns across distinct BC cell subpopulations. Functional validation in vitro demonstrated that knockdown of metadherin (MTDH), a key MMAG, significantly suppressed BC cell proliferation and invasion, as evidenced by cell proliferation, colony formation, wound healing, and Transwell migration assays. The MMAG-based scoring system effectively stratified patients into high- and low-risk groups with independent prognostic value, and immune infiltration analysis revealed marked differences in the tumor microenvironment between risk groups. Collectively, our findings establish a novel MMAG-based prognostic framework for BC and identify MTDH as a critical regulator of tumor progression, highlighting its potential as a therapeutic target.
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BibTeX
@article{wang2026comprehensive,
title = {{Comprehensive analysis of mitochondrial metabolism–associated clusters and prognostic scoring model index construction in breast cancer}},
author = {Chen Wang and Xiaofan Wu and Jingkun Wang and Haojun Xuan and Chenlu Liang and Liuyi Li and Hongjian Yang and Shusen Zheng},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-63822-3},
url = {https://doi.org/10.1038/s41598-026-63822-3},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comprehensive analysis of mitochondrial metabolism–associated clusters and prognostic scoring model index construction in breast cancer
AU - Chen Wang
AU - Xiaofan Wu
AU - Jingkun Wang
AU - Haojun Xuan
AU - Chenlu Liang
AU - Liuyi Li
AU - Hongjian Yang
AU - Shusen Zheng
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-63822-3
UR - https://doi.org/10.1038/s41598-026-63822-3
AB - Further stratification of breast cancer (BC) prognosis is of considerable clinical importance, yet the mechanistic role of mitochondrial metabolism in BC progression remains incompletely understood. In this study, we systematically identified mitochondrial metabolism–associated genes (MMAGs) linked to BC prognosis by integrating clinical survival data and developed an MMAG-based risk scoring system using univariate and multivariate Cox regression combined with least absolute shrinkage and selection operator (LASSO) analysis. We characterized the relationship between MMAG-defined clusters, immune microenvironment infiltration, and clinicopathological features, and employed single-cell RNA sequencing to delineate MMAG expression patterns across distinct BC cell subpopulations. Functional validation in vitro demonstrated that knockdown of metadherin (MTDH), a key MMAG, significantly suppressed BC cell proliferation and invasion, as evidenced by cell proliferation, colony formation, wound healing, and Transwell migration assays. The MMAG-based scoring system effectively stratified patients into high- and low-risk groups with independent prognostic value, and immune infiltration analysis revealed marked differences in the tumor microenvironment between risk groups. Collectively, our findings establish a novel MMAG-based prognostic framework for BC and identify MTDH as a critical regulator of tumor progression, highlighting its potential as a therapeutic target.
SN - 2045-2322
ER -