Determining the metabolomic fingerprint of premalignant lesions in endometrial cancer for early diagnosis and screening

Description

Background

Endometrial cancer is the sixth most common cancer among women, with ~417,000 new cases diagnosed globally in 2020. Women have a 3% lifetime risk of developing endometrial cancer. While mortality rates for other cancers are declining, endometrial cancer related mortality is increasing. Early diagnosis is crucial for timely treatment and improved survival rates. Atypical endometrial hyperplasia describes the premalignant transformation of the lining of the womb, which will progress to endometrial cancer in 60% of cases. Early detection of atypical endometrial hyperplasia would allow for clinical intervention before malignant transformation, thus significantly reducing the incidence of endometrial cancer.

We hypothesise that metabolic changes in healthy postmenopausal, atypical endometrial hyperplasia and endometrial cancer can be detected by small molecule profiling of uterine secretions. The findings from this PhD will be invaluable in the pursuit of preventative screening and novel treatment strategies for endometrial cancer.

Aims of PhD:

1. Define the metabolomic signature of uterine secretions collected using a vaginal tampon biospecimen from postmenopausal (healthy), atypical endometrial hyperplasia and endometrial cancer cohorts.
2. Assess discriminatory power of metabolomic biomarkers to enable optimal classification of healthy, atypical endometrial hyperplasia and endometrial cancer.
3. To validate metabolomic changes observed from the analysis of vaginal fluid in endometrial epithelial organoid cultures: endometrial epithelial organoids will be derived from primary endometrial biopsies using established protocols.

Training opportunities:

All Postgraduate students attending the University of Liverpool will participate in a flexible programme as part of their PhD that supports all postgraduate research students with their on-going professional and personal development. This central programme has been designed to provide a range of opportunities that effectively help prepare PGRs in becoming successful researchers and plan for their future careers (main themes include Taking Ownership of your PhD; Resilience; Research writing; Presentation skills; Research Productivity; Creative & Critical Thinking and Careers).

All well designed metabolomic studies have significant opportunities to gain experience and expertise in the metabolomic analytical pipeline. Liverpool is ideally placed to enable this as it is home to the Liverpool Training Centre for Metabolomics (only three Centres in England) and the successful candidate will attend relevant training offered here. Main areas of training will include:

Cell biology – tissue culture techniques including advanced organoid culture.

Analytical chemistry – sample preparation, liquid chromatography, mass spectrometry (high resolution accurate mass spectrometry and targeted quantitative tandem mass spectrometry).

Data analysis – unsupervised and supervised statistical analysis, modelling data and diagnostic performance characteristics.

Metabolism – studying human metabolism in health and disease, specifically endometrial cancer.

Translational research – to be part of the discovery and validation of a set of biomarkers that could be used to help patients through evaluation of a large clinical trial.

Networking – local level: clinical and university laboratories and through Liverpool Doctoral College; Nationally: conferences.

Qualifications

Eligible candidates will have a BSc (minimum of a 2:1), and will have or be due to obtain, a Master’s Degree related to Molecular Biology, Biochemistry or Chemistry. Experience in metabolomics, mass spectrometry or organoid culture are desirable but not essential.

Applying

Applications should be made to project supervisors in the first instance via CV and cover letter. This is for all applications. Only when a candidate has been selected following interview will a formal online application be required.