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<p>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.</p>

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Comprehensive analysis of mitochondrial metabolism–associated clusters and prognostic scoring model index construction in breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月30日

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  • Chen Wang,
  • Xiaofan Wu,
  • Jingkun Wang,
  • Haojun Xuan,
  • Chenlu Liang,
  • Liuyi Li,
  • Hongjian Yang,
  • Shusen Zheng

摘要

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.