With current standard-of-care treatments, approximately 20% of stage II and 36% of stage III colon cancer (CC) patients will experience disease relapse following surgery. Molecular and histological subtyping of CC has identified a poor-prognostic group of patients characterised by high levels of epithelial-to-mesenchymal transition (EMT) signalling and an abundance of stroma (particularly fibroblasts) in their tumour microenvironment. To date, there has been inconsistent data regarding the benefit of standard chemotherapy in these patients with high-fibroblast (HiFi) tumours. Additionally, there is limited understanding of the specific biological signalling driving relapse in HiFi tumours. This study provides evidence to support the hypothesis that the EMT signalling seen in the poor-prognostic CC patients is due to increased levels of stromal cells present in their tumour samples, rather than increased epithelial cells undergoing EMT. A number of previously defined prognostic assays for CC identify these HiFi tumours, although when the HiFi group is assessed on their own, previously-defined prognostic biology fails to stratify patients based on relapse. To address this, work presented here describes the development, testing and independent validation of a novel seven-gene HiFi-specific prognostic signature.
| Date of Award | Jul 2021 |
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| Original language | English |
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| Awarding Institution | - Queen's University Belfast
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| Sponsors | Cancer Research UK |
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| Supervisor | Mark Lawler (Supervisor), Philip Dunne (Supervisor) & Manuel Salto-Tellez (Supervisor) |
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- Cancer
- colorectal cancer
- colon cancer
- cancer-associated fibroblasts
- tumour microenvironment
- tumour stroma
- immune modulation
- antigen processing and presentation
- polyinosinic:polycytidylic acid
- poly(I:C)
- toll-like receptor 3
- TLR3
- gene expression signature
- prognostic signature
- epithelial–mesenchymal transition
- EMT
- molecular pathology
- STAT1
- translational
Defining the clinical importance of epithelial-stroma-immune signalling in colorectal cancer using a molecular pathology approach
McCorry, A. (Author). Jul 2021
Student thesis: Doctoral Thesis › Doctor of Philosophy