Enhancing Early Detection of Oesophageal Squamous Cell Carcinoma Through Shallow Whole-Genome Sequencing and Non-Endoscopic Sponge Sampling
type: CreativeWork
description: The incidence of oesophageal squamous cell carcinoma (OSCC) remains high, accounting for approximately 90% of the nearly half-million annual cases of oesophageal cancer globally. Although effective, conventional upper endoscopy is invasive and costly, limiting its widespread use for screening high-risk populations and surveillance of at-risk individuals, including those with a history of head and neck cancer. In this thesis, I explored the potential of shallow whole-genome sequencing (sWGS) to detect genome-wide copy number alterations (CNAs) in cells collected using a non-endoscopic sponge pan-oesophageal sampling device (Cytosponge) for the early detection of OSCC and its precursor lesions, oesophageal squamous cell dysplasia (OSD). To achieve this, I utilised previously unexamined samples from two prospective studies: the Early Detection and Surveillance of Oesophageal Cancer with Cytosponge and Nucleic Acid Biomarkers (EDEN) study and the Oesophageal Squamous cell CARcinoma (OSCAR) project. Across both studies, I analysed 242 oesophageal specimens collected using the Cytosponge device from 178 participants, comprising early stage OSCC (n = 71), high-risk individuals (n = 75), and healthy controls with dyspeptic symptoms (n = 96). These samples underwent 1.5-2x sWGS, alongside standard pathological assessment including haematoxylin & eosin (H&E) staining for atypia detection and p53 immunohistochemistry (IHC). For the first time, I demonstrated the feasibility of detecting CNAs indicative of OSD and early cancer from non-micro-dissected, pan-oesophageal Cytosponge samples. My novel genomic approach integrated chromosome arm-level CNAs with a new metric, the genome-wide instability score (GWIS), which quantifies genomic instability across the entire genome. Using a generalised linear model with elastic net regularisation, I identified specific alterations in chromosome arms 2q, 3q, 9p, and 11q, along with the GWIS, as significant predictors of OSD and early OSCC. …
abstract: The incidence of oesophageal squamous cell carcinoma (OSCC) remains high, accounting for approximately 90% of the nearly half-million annual cases of oesophageal cancer globally. Although effective, conventional upper endoscopy is invasive and costly, limiting its widespread use for screening high-risk populations and surveillance of at-risk individuals, including those with a history of head and neck cancer. In this thesis, I explored the potential of shallow whole-genome sequencing (sWGS) to detect genome-wide copy number alterations (CNAs) in cells collected using a non-endoscopic sponge pan-oesophageal sampling device (Cytosponge) for the early detection of OSCC and its precursor lesions, oesophageal squamous cell dysplasia (OSD). To achieve this, I utilised previously unexamined samples from two prospective studies: the Early Detection and Surveillance of Oesophageal Cancer with Cytosponge and Nucleic Acid Biomarkers (EDEN) study and the Oesophageal Squamous cell CARcinoma (OSCAR) project. Across both studies, I analysed 242 oesophageal specimens collected using the Cytosponge device from 178 participants, comprising early stage OSCC (n = 71), high-risk individuals (n = 75), and healthy controls with dyspeptic symptoms (n = 96). These samples underwent 1.5-2x sWGS, alongside standard pathological assessment including haematoxylin & eosin (H&E) staining for atypia detection and p53 immunohistochemistry (IHC). For the first time, I demonstrated the feasibility of detecting CNAs indicative of OSD and early cancer from non-micro-dissected, pan-oesophageal Cytosponge samples. My novel genomic approach integrated chromosome arm-level CNAs with a new metric, the genome-wide instability score (GWIS), which quantifies genomic instability across the entire genome. Using a generalised linear model with elastic net regularisation, I identified specific alterations in chromosome arms 2q, 3q, 9p, and 11q, along with the GWIS, as significant predictors of OSD and early OSCC. …
author: Yusuf, Aishat
language: eng
keywords: Oesophageal squamous cell carcinoma, Minimally invasive sampling, Genomics and copy number alterations, Early cancer detection, Cytosponge biomarkers
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/1c1a046e-443a-49eb-8aaf-74240292d230/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2024-09-24
date modified: 2026-07-22T22:24:08Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.116441