Sehgal, M and Ramu, S and Vaz, JM and Ganapathy, YR and Muralidharan, S and Venkatraghavan, S and Jolly, MK (2024) Characterizing heterogeneity along EMT and metabolic axes in colorectal cancer reveals underlying consensus molecular subtype-specific trends. In: Translational Oncology, 40 .
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Abstract
Colorectal cancer (CRC) is highly heterogeneous with variable survival outcomes and therapeutic vulnerabilities. A commonly used classification system in CRC is the Consensus Molecular Subtypes (CMS) based on gene expression patterns. However, how these CMS categories connect to axes of phenotypic plasticity and heterogeneity remains unclear. Here, in our analysis of CMS-specific TCGA data and 101 bulk transcriptomic datasets, we found the epithelial phenotype score to be consistently positively correlated with scores of glycolysis, OXPHOS and FAO pathways, while PD-L1 activity scores positively correlated with mesenchymal phenotype scoring, revealing possible interconnections among plasticity axes. Single-cell RNA-sequencing analysis of patient samples revealed that that CMS2 and CMS3 subtype samples were relatively more epithelial as compared to CMS1 and CMS4. CMS1 revealed two subpopulations: one close to CMS4 (more mesenchymal) and the other closer to CMS2 or CMS3 (more epithelial), indicating a partial EMT-like behavior. Consistent observations were made in single-cell analysis of metabolic axes and PD-L1 activity scores. Together, our results quantify the patterns of two functional interconnected axes of phenotypic heterogeneity � EMT and metabolic reprogramming � in a CMS-specific manner in CRC. © 2023
| Item Type: | Journal Article |
|---|---|
| Publication: | Translational Oncology |
| Publisher: | Neoplasia Press, Inc. |
| Additional Information: | The copyright for this article belongs to authors. |
| Keywords: | programmed death 1 ligand 1; transcriptome; transforming growth factor, Article; cancer survival; cell plasticity; colorectal cancer; consensus; entropy; epithelial mesenchymal transition; gene expression; gene overexpression; gene set enrichment analysis; genetic heterogeneity; glycolysis; immune evasion; mesenchyme; metabolic regulation; nuclear reprogramming; oxidative phosphorylation; phenotype; phenotypic plasticity; progression free survival; RNA sequence; single cell analysis; single cell RNA seq; tissue microarray; transcriptomics |
| Department/Centre: | Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering |
| Date Deposited: | 28 Feb 2024 13:18 |
| Last Modified: | 28 Feb 2024 13:18 |
| URI: | https://eprints.iisc.ac.in/id/eprint/83705 |
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