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The identification of tissue and blood-based DNA methylation biomarkers for risk stratification in prostate cancer.

School of Medicine, Dentistry and Biomedical Sciences | PHD

Applications are now CLOSED
Funding
Funded
Reference Number
SMED-2251-1028
Application Deadline
25 February 2025
Start Date
1 October 2025

Overview

Prostate cancer is the most common cancer among men in the UK, with over 52,000 cases and 12,000 deaths annually, representing a substantial healthcare challenge. Its varied clinical outcomes necessitate improved diagnostic and treatment strategies to enhance survival rates while preserving quality of life. Current diagnostic methods, such as the Prostate-Specific Antigen (PSA) test, lack specificity, leading to overdiagnosis and overtreatment. While advances like multiparametric MRI and molecular tissue tests have improved diagnostic accuracy, distinguishing aggressive prostate cancers from indolent ones remains difficult. Emerging evidence highlights the potential of epigenetic markers, particularly DNA methylation, as superior biomarkers for prostate cancer. Circulating tumour DNA (ctDNA) methylation profiling offers higher sensitivity and specificity compared to traditional genomic methods. This approach identifies genome-wide methylation changes associated with prostate cancer progression and addresses current diagnostic limitations. Liquid biopsies leveraging ctDNA provide a minimally invasive tool for real-time monitoring of disease progression. They enable early relapse detection, minimal residual disease identification post-treatment and tracking of treatment response by analysing methylation patterns reflecting cancer-specific signals. This project aims to develop blood-based DNA methylation biomarkers to enhance prostate cancer risk stratification and early relapse detection, paving the way for more precise, effective and patient-centered care.

Transforming Prostate Cancer Diagnosis and Management Through Liquid Biopsies
Prostate cancer is the most common cancer among men in the UK, with over 52,000 new cases and 12,000 deaths annually. The current diagnostic landscape is primarily dominated by the Prostate-Specific Antigen (PSA) test, which suffers from low specificity, leading to over-treatment and misdiagnosis. Advanced techniques, including multiparametric MRI and tissue-based molecular tests, have improved diagnostic pathways but still struggle to distinguish aggressive cancers, requiring urgent intervention, from indolent cancers, which may not necessitate immediate treatment. This unmet clinical need highlights the necessity for innovative solutions to enhance early detection, risk stratification and treatment monitoring, while minimising the impact on patients’ quality of life.

Liquid Biopsies and Epigenetic Insights
Liquid biopsies represent a revolutionary approach to cancer detection, offering a minimally invasive and real-time method to monitor disease progression. By analysing circulating tumour DNA (ctDNA) in blood samples, we aim to identify DNA methylation patterns specific to prostate cancer. These epigenetic markers reflect tumour origin and activity, providing superior sensitivity and specificity compared to traditional genomic methods. Traditional DNA methylation protocols, such as bisulfite conversion, often degrade sugstantial amounts of DNA, which limits their effectiveness. In contrast, this project adopts an enzymatic conversion-based method which preserves a larger quantity of circulating free DNA (cfDNA), thereby enhancing the ability to detect low abundance ctDNA. To further increase sensitivity, we employ Droplet Digital PCR (ddPCR), which partitions DNA into approximately 20,000 individual reactions. This method allows for unparalleled sensitivity and precision in detecting rare sequence variants, even against a backdrop of high-abundance DNA, overcoming the limitations faced by standard quantitative PCR.

Key Aims:
1. Early Relapse Detection: We aim to identify blood-based methylation markers that can detect minimal residual disease after treatment, allowing for earlier and more accurate predictions of relapse compared to the PSA test.
2. Treatment Monitoring: By evaluating dynamic changes in ctDNA methylation patterns, we seek to gain insights into treatment response and resistance, enabling the development of personalized care strategies tailored to individual patient needs.
3. Enhanced Risk Stratification: Our goal is to integrate ctDNA methylation analysis with PSA testing to improve the identification of high-risk patients. This will allow for tailored interventions that maximize both survival rates and quality of life.
Impact
This innovative project opens new avenues for identifying epigenetic biomarkers, facilitating the development of highly sensitive, accurate and non-invasive diagnostic solutions for risk stratification and disease monitoring in prostate cancer. The ultimate objective is to seamlessly integrate liquid biopsies into clinical practice, transforming the current diagnostic paradigm into a more patient-centered care model. By improving early detection and treatment personalisation, this approach has the potential to significantly enhance patient outcomes and reduce the burden of prostate cancer on individuals and healthcare systems alike.

Funding Information

Funded by the Department for the Economy (DfE). For eligible students the value of an award includes the cost of approved tuition fees and maintenance support the 2025/26 rates are still to be confirmed (current rates for 2024/25 are Fees £4,786, Stipend £19,237).

For further information about eligibility criteria please refer to the DfE Postgraduate Studentship Terms and Conditions at https://www.economy-ni.gov.uk/publications/student-finance-postgraduate-studentships-terms-and-conditions

Project Summary
Supervisor

Dr Laura Feeney


Mode of Study

Full-time: 3 Years


Funding Body
DfE
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