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Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines
Published on: March 17, 2023
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The Heterogeneous Interplay Between Metabolism and Mitochondrial Activity in Colorectal Cancer
Christophe Desterke1, Yuanji Fu2, Jorge Mata-Garrido2
1Faculty of Medicine, University Paris Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM) Unit UMRS-1310, 94800 Villejuif, France.
Journal of Personalized Medicine
|December 24, 2025
Summary
Colorectal cancer exhibits metabolic heterogeneity linked to mitochondrial activity. New R-packages reveal distinct metabolic profiles in tumor subtypes, aiding personalized cancer therapy development.
Area of Science:
- Oncology
- Metabolic Engineering
- Bioinformatics
Background:
- Colorectal cancer (CRC) is a heterogeneous malignancy influenced by genetic, environmental, nutritional, and lifestyle factors.
- CRC is often characterized by a Warburg metabolic phenotype, with increased glycolysis over oxidative phosphorylation.
- Understanding metabolic heterogeneity and mitochondrial activity is crucial for CRC research.
Purpose of the Study:
- To develop and utilize R-packages for exploring metabolic and mitochondrial activities in CRC transcriptomics data.
- To investigate the relationship between metabolic profiles, mitochondrial function, and CRC subtypes.
- To identify potential biomarkers for personalized therapeutic strategies in CRC.
Main Methods:
- Development of two R-packages, keggmetascore and mitoscore, for analyzing KEGG metabolism and Mitocarta V3 annotations.
- Application of packages to bulk and single-cell RNA-sequencing data from CRC samples.
- Utilized machine learning (Elastic-net) for predictive modeling and integrated multi-modal data analysis.
Main Results:
- Metformin stimulation regulated metabolism and mitochondrial activity in LOVO cells.
- Single-cell analysis revealed activated metabolism/mitochondria in MSI-high tumors and repressed in POLE-mutated tumors.
- Bulk analysis showed reduced metabolism/mitochondria in CRC vs. normal tissues; BRAF-V600E mutations correlated with repressed metabolism and fewer mitochondrial interactions.
- A novel metabolism/mitochondrial activity score predicted CMS1-MSI subtype, metastatic status, and BRAF-V600E mutation.
Conclusions:
- Mitochondrial metabolism plays a pivotal role in colorectal cancer subtyping.
- Metabolic and mitochondrial activity profiles serve as valuable predictive biomarkers for personalized CRC therapies.
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