Normal tissue transcriptional signatures for tumor-type-agnostic phenotype prediction
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View abstract on PubMed
Summary
This summary is machine-generated.Cancer cells repurpose normal tissue gene expression patterns, creating distinct transcriptomic archetypes. These patterns influence tumor characteristics, patient survival, and drug response, offering a new framework for understanding cancer heterogeneity.
Area Of Science
- Genomics
- Cancer Biology
- Bioinformatics
Background
- Cancer exhibits diverse transcriptional patterns, but the origin of this heterogeneity is not fully understood.
- Shared transcriptomic signatures across cancers may stem from normal tissue functions.
Purpose Of The Study
- To investigate if normal tissue transcriptomic profiles can explain cancer phenotype heterogeneity.
- To identify and characterize transcriptomic archetypes in normal and cancerous tissues.
Main Methods
- Non-negative matrix factorization applied to normal tissue transcriptomic data.
- Derivation of six distinct transcriptomic archetypes.
- Analysis of archetype enrichment in various malignancies and correlation with clinical data.
Main Results
- Six transcriptomic archetypes were identified, describing both normal tissue and cancer patterns.
- Archetype enrichment correlated with tumor characteristics, patient survival, and drug sensitivity, independent of DNA alterations.
- Metastatic breast cancers showed transcriptomic signatures resembling invaded tissues.
Conclusions
- Cancer cells appropriate normal tissue transcriptomic characteristics for progression and drug response.
- This quantitative framework aids in understanding cancer phenotype diversity and may inform patient management.
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