Measuring and Modelling the Epithelial- Mesenchymal Hybrid State in Cancer: Clinical Implications

Jolly, Mohit Kumar; Murphy, Ryan J; Bhatia, Sugandha; Whitfield, Holly J.; Redfern, Andrew; Davis, Melissa J.; Thompson, Erik W.

doi:10.1159/000515289

Cited by 35 publications

(35 citation statements)

References 177 publications

(249 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ability of hybrid E/M cells to form clusters of CTCs can also escalate their metastatic fitness, given the disproportionately high metastatic burden of CTC clusters [ 26 , 27 , 28 ]. Given the context-specific diversity of hybrid E/M phenotypes [ 29 ], it is imperative that EMP be quantified as a continuum or spectrum, through integrating various experimental and/or computational methods.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic-Based Quantification of the Epithelial-Hybrid-Mesenchymal Spectrum across Biological Contexts

et al. 2021

Self Cite

View full text Add to dashboard Cite

Epithelial-mesenchymal plasticity (EMP) underlies embryonic development, wound healing, and cancer metastasis and fibrosis. Cancer cells exhibiting EMP often have more aggressive behavior, characterized by drug resistance, and tumor-initiating and immuno-evasive traits. Thus, the EMP status of cancer cells can be a critical indicator of patient prognosis. Here, we compare three distinct transcriptomic-based metrics—each derived using a different gene list and algorithm—that quantify the EMP spectrum. Our results for over 80 cancer-related RNA-seq datasets reveal a high degree of concordance among these metrics in quantifying the extent of EMP. Moreover, each metric, despite being trained on cancer expression profiles, recapitulates the expected changes in EMP scores for non-cancer contexts such as lung fibrosis and cellular reprogramming into induced pluripotent stem cells. Thus, we offer a scoring platform to quantify the extent of EMP in vitro and in vivo for diverse biological applications including cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Transcriptomic-Based Quantification of the Epithelial-Hybrid-Mesenchymal Spectrum across Biological Contexts

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The ability of hybrid E/M cells to form clusters of CTCs can also escalate their metastatic fitness, given the disproportionately high metastatic burden of CTC clusters (Aceto et al, 2014;Cheung et al, 2016;. Given the context-specific diversity of hybrid E/M phenotypes (Jolly et al, 2021), it is imperative that EMP be quantified as a continuum or spectrum, through integrating various experimental and/or computational methods.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic-based quantification of the epithelial-hybrid-mesenchymal spectrum across biological contexts

Mandal

Tejaswi

Janivara

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Epithelial-mesenchymal plasticity (EMP) underlies embryonic development, wound healing, and cancer metastasis and fibrosis. Cancer cells exhibiting EMP often have more aggressive behavior, characterized by drug resistance, and tumor-initiating and immuno-evasive traits. Thus, the EMP status of cancer cells can be a critical indicator of patient prognosis. Here, we compare three distinct transcriptomic-based metrics - each derived using a different gene list and algorithm - that quantify the EMP spectrum. Our results for 96 cancer-related RNA-seq datasets reveal a high degree of concordance among these metrics in quantifying the extent of EMP. Moreover, each metric, despite being trained on cancer expression profiles, recapitulates the expected changes in EMP scores for non-cancer contexts such as lung fibrosis and cellular reprogramming into induced pluripotent stem cells. Thus, we offer a scoring platform to quantify the extent of EMP in vitro and in vivo for diverse biological applications including cancer.

show abstract

“…In epithelial tumours, malignant cells can undergo an epithelial to mesenchymal transition (EMT) and acquire mesenchymal properties such as migration and motility. The process of EMT is thought to enable cancers to metastasise 50 . While often characterised as a single process, the transition from an epithelial to mesenchymal phenotype involves various complex changes to cells and their microenvironment 51 .…”

Section: Resultsmentioning

confidence: 99%

vissE: A versatile tool to identify and visualise higher-order molecular phenotypes from functional enrichment analysis

Bhuva

Tan

Liu

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Functional analysis of high throughput experiments using pathway analysis is now ubiquitous. Though powerful, these methods often produce thousands of redundant results owing to knowledgebase redundancies upstream. This scale of results hinders extensive exploration by biologists and often leads to investigator biases due to previous knowledge and expectations. To address this issue, we present vissE, a flexible network-based analysis method that summarises redundancies into biological themes and provides various analytical modules to characterise and visualise them with respect to the underlying data, thus providing a comprehensive view of the biological system. We demonstrate vissE's versatility by applying it to three different technologies: bulk, single-cell and spatial transcriptomics. Applying vissE to a factor analysis of a breast cancer spatial transcriptomic data, we identified stromal phenotypes that support tumour dissemination. Its adaptability allows vissE to enhance all existing gene-set enrichment and pathway analysis workflows, removing investigator bias from molecular discovery.

show abstract

Measuring and Modelling the Epithelial- Mesenchymal Hybrid State in Cancer: Clinical Implications

Cited by 35 publications

References 177 publications

Transcriptomic-Based Quantification of the Epithelial-Hybrid-Mesenchymal Spectrum across Biological Contexts

Transcriptomic-Based Quantification of the Epithelial-Hybrid-Mesenchymal Spectrum across Biological Contexts

Transcriptomic-based quantification of the epithelial-hybrid-mesenchymal spectrum across biological contexts

vissE: A versatile tool to identify and visualise higher-order molecular phenotypes from functional enrichment analysis

Contact Info

Product

Resources

About