Comparative analysis of sporadic and colitis associated cancers
File(s)
Author(s)
Roberts, Duncan
Type
Thesis
Abstract
Colitis associated cancers (CACs) are a sequelae of inflammatory bowel disease (IBD) which is difficult to detect during surveillance, leading to high rates of interval cancers. Despite the well defined risk factor of IBD in the development of cancer, and the frequent application of metataxonomic and mass spectrometry techniques for investigation to IBD, little is known about the structure and function of the microbiota in CAC, features of tissue level metabolism, or whether patient risk can be identified.
Open access multi-omics data in patients with long disease duration (>10 years) was analysed to identify potential risk factors. Potential alterations in stool bile acid concentrations not explained by diet were identified, as well as transcriptional differences in uninvolved ileum between patients with over or under 10 years IBD duration. However these may be related recruitment sites.
A novel tool to predict the function of the microbiota was developed and benchmarked against state of the art techniques, finding that prediction accuracy is a function of metagenome size, and remains stable with growing database size.
A prospective cohort of patients undergoing colonic resection for IBD, CAC, and sporadic CRC were recruited and a comprehensive analysis of the tissue-associated microbiota undertaken by 16S rRNA gene sequencing. A depletion of Fusobacterium in CAC tumour sites was confirmed, and potential taxa of interest identified.
Mass spectrometry imaging of CAC tumours was performed for the first time, with features suggestive of less intra-tumour heterogeneity than sporadic CRC. Supervised classification of tumours was performed using both metataxonomic and metabolomic datasets, but both performed poorly.
Open access multi-omics data in patients with long disease duration (>10 years) was analysed to identify potential risk factors. Potential alterations in stool bile acid concentrations not explained by diet were identified, as well as transcriptional differences in uninvolved ileum between patients with over or under 10 years IBD duration. However these may be related recruitment sites.
A novel tool to predict the function of the microbiota was developed and benchmarked against state of the art techniques, finding that prediction accuracy is a function of metagenome size, and remains stable with growing database size.
A prospective cohort of patients undergoing colonic resection for IBD, CAC, and sporadic CRC were recruited and a comprehensive analysis of the tissue-associated microbiota undertaken by 16S rRNA gene sequencing. A depletion of Fusobacterium in CAC tumour sites was confirmed, and potential taxa of interest identified.
Mass spectrometry imaging of CAC tumours was performed for the first time, with features suggestive of less intra-tumour heterogeneity than sporadic CRC. Supervised classification of tumours was performed using both metataxonomic and metabolomic datasets, but both performed poorly.
Version
Open Access
Date Issued
2024-04-30
Date Awarded
01/05/2025
Advisor
Kinross, James
Ford, Lauren
Marchesi, Julian
Takats, Zoltan
Sponsor
Merck & Co. (Firm)
Medical Research Council (Great Britain)
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)