Pan-cancer association of a mitochondrial function score with genomic alterations and clinical outcome

Q: What is MitoScore and how is it calculated?

MitoScore is a quantitative metric of mitochondrial function built by summing normalized expression levels of six mitochondrial genes reported as consistently altered across multiple cancers.

Q: How does MitoScore relate to tumor versus normal tissues?

MitoScore is significantly higher in tumor tissues than in adjacent normal tissues across most cancer types.

Q: Can MitoScore predict clinical outcomes?

Yes. High MitoScore is associated with worse prognosis in several cancer types, supporting its role as a predictive biomarker for clinical outcomes.

Sep 21, 2026

Uploaded by Genevieve

MitoScore is introduced and validated as a quantitative metric of mitochondrial function across multiple cancer types. Using TCGA gene-expression data from 24 cancers and matched normal tissues, the score is computed by summing normalized expression of six mitochondrial genes consistently altered in pan-cancer contexts. DESeq2 identifies differential mitochondrial-function related changes, while Spearman correlation, linear regression, and Kaplan–Meier analyses evaluate links to tumor proliferation, hypoxia, aneuploidy, and clinical outcomes. MitoScore is higher in tumors, associates with aggressive biology, and predicts poorer prognosis in multiple cancers.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Methods

TCGA dataset

MitoScore construction and differential expression

Statistical analyses and survival assessment

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Pan-cancer association of a mitochondrial function score with genomic alterations and clinical outcome Shikun Zhu1,3, Chen Chen1,3, Min Wang1,3, Yue Liu1,3, Baolin Li1, Xing Qi1,2, Miao Song1, Xuexue Liu1, Jia Feng1􀀍 & Jinbo Liu1􀀍 Mitochondria are pivotal in cellular energy metabolism and have garnered significant attention for their roles in cancer progression and therapy resistance. Despite this, the functional diversity of mitochondria across various cancer types remains inadequately characterized. This study seeks to fill this knowledge gap by introducing and validating MitoScore—a novel metric designed to quantitatively assess mitochondrial function across a wide array of cancers. Our investigation evaluates the capacity of MitoScore not only to distinguish between tumor and adjacent normal tissues but also to serve as a predictive marker for clinical outcomes. We analyzed gene expression data from 24 cancer types and corresponding normal tissues using theTCGA database. MitoScore was calculated by summing the normalized expression levels of six mitochondrial genes known to be consistently altered across multiple cancers. Differential gene expression was assessed using DESeq2, with a focus on identifying significant changes in mitochondrial function. MitoScore’s associations with tumor proliferation, hypoxia, aneuploidy, and clinical outcomes were evaluated using Spearman’s correlation, linear regression, and Kaplan–Meier survival analyses. MitoScore was significantly higher in tumor tissues compared to normal tissues across most cancer types (p < 0.001). It positively correlated with tumor proliferation rates (r =0.46), hypoxia scores (r =0.61), and aneuploidy (r =0.44), indicating its potential as a marker of aggressive tumor behavior. High MitoScore was also associated with poorer prognosis in several cancer types, suggesting its utility as a predictive biomarker for clinical outcomes. This study introduces MitoScore, a metric for mitochondrial activity often elevated in tumors and linked to poor prognosis. It correlates positively with hypoxia and negatively with stromal and immune infiltration, highlighting mitochondria’s role in the tumor microenvironment. MitoScore’s association with genomic instability, such as aneuploidy, suggests mitochondrial dysfunction contributes to cancer progression. Despite challenges in mitochondrial-targeted therapies, MitoScore may identify tumors responsive to such treatments, warranting further research for clinical application. Mitochondria play a complex and crucial role in cellular biology and cancer development1. Beyond their wellknown function as the cell’s powerhouse, generating ATP through oxidative phosphorylation, mitochondria are involved in various critical cellular processes, including apoptosis and metabolic regulation2–4. In the context of cancer, mitochondrial dysfunction has been widely recognized as a key factor contributing to tumorigenesis5,6, progression7, and the development of drug resistance8–10. Alterations in mitochondrial function are often associated with the metabolic reprogramming of tumor cells. Cancer cells tend to rely on glycolysis for energy production, even in the presence of sufficient oxygen—a phenomenon known as the “Warburg effect”11, 12. Moreover, mitochondria play a vital role in maintaining cellular redox balance and producing reactive oxygen species (ROS), which are critical mediators of cell signaling and regulation of cell death13–15. Mitochondrial dysfunction can lead to abnormal ROS levels, resulting in DNA damage, altered gene expression, and ultimately, cancer development16, 17. 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, Sichu

FAQs

What is MitoScore and how is it calculated?

MitoScore is a quantitative metric of mitochondrial function built by summing normalized expression levels of six mitochondrial genes reported as consistently altered across multiple cancers.

How does MitoScore relate to tumor versus normal tissues?

MitoScore is significantly higher in tumor tissues than in adjacent normal tissues across most cancer types.

Can MitoScore predict clinical outcomes?

Yes. High MitoScore is associated with worse prognosis in several cancer types, supporting its role as a predictive biomarker for clinical outcomes.

Sep 21, 2026

Uploaded by Genevieve