STEMOVA

Characterisation of the STEroid Metabolome in mucinous OVArian cancer.

The University of Birmingham Institute of Cancer and Genomics Sciences is looking to develop better tests for ovarian cancer. This study will help us find out how well new types of medical tests diagnose ovarian cancer. 

Background

Ovarian cancer is a serious type of cancer that affects women, and it’s especially dangerous because it’s hard to detect early. The chances of surviving ovarian cancer greatly depend upon when it’s found. If caught early, there’s a good chance of surviving for at least 5 years after diagnosis. But if it’s found at a later stage, the chances of surviving drop significantly. 

One rare (~2-3% of all ovarian cancers) type of epithelial ovarian cancer called mucinous ovarian cancer tends to affect younger women. It can sometimes be found early, which is good for survival rates, but if it's discovered late, it's much harder to treat. Unfortunately, the current tests for mucinous ovarian cancer aren't very accurate, so we are looking for new ways to detect it earlier. 

This study focuses on understanding how certain hormones in the body might be linked to mucinous ovarian cancer. We will collect urine samples from different women, including those with ovarian cancer and those without, to study these hormones. Earlier research has found that certain patterns in these hormones might help detect mucinous ovarian cancer earlier. 

Overall, by studying hormones in the body, we might find better ways to detect ovarian cancer sooner, which could help save lives. 

Reasoning

Past research has found that changes in certain hormones, the immune system, and how genes work might be linked to ovarian cancer, but we don't fully understand how yet. We want to use advanced tools to look for signs of cancer in samples from patients with different kinds of ovarian and bowel tumours. These tools can help us find special markers that might show if someone has cancer, especially the mucinous type mentioned earlier. We'll collect samples like urine and tissue from these patients and use new technologies to analyse them. This could help us find new ways to detect ovarian cancer early, which would be important for helping patients get better treatment.

Hormonal therapy works well to treat certain types of ovarian cancer. However, we still don't fully understand how hormone pathways work in ovarian cancer, including mucinous ovarian cancer. 

In our past research, we looked at the levels of certain hormones in the urine of healthy women and women being tested for ovarian cancer. We found that five specific hormone markers related to early hormone production were higher in women with mucinous ovarian cancer compared to healthy people or those with non-cancerous tumours. We also noticed that these hormone levels increased as the tumours became more severe, suggesting that hormone pathways might be involved in the development of mucinous ovarian cancer. 

Research Aims

• We will study how hormones are produced in mucinous ovarian cells grown in the lab, and in models made from tissue donated by participants.
• We will analyse the genes active in mucinous ovarian cancer by studying a dataset available to the public.
  1. This dataset includes information on benign tumours, borderline tumours, and cancerous tumours. We want to understand how the levels of certain genes might relate to different aspects of the cancer.
  2. We will examine the levels of hormones in urine collected over 24 hours from people with mucinous ovarian cancer, borderline tumours, non-cancerous ovarian tumours, and mucinous tumours from the appendix. This will help us understand if there are differences in hormone levels that could be related to these types of tumours. 

Study Design

Sub-Study 1 - Diagnostic: 

In the first part of the study, we're going to involve multiple medical centres in a research project. Our goal is to expand on a previous study about the hormones found in urine to specifically look at mucinous ovarian cancer, as well as mucinous benign tumours and borderline tumours. 

We're planning to recruit a total of 265 people for this study. Out of these, around 25 individuals are expected to be diagnosed with mucinous ovarian cancer eventually. 

We'll be examining the urine samples of these participants using a technique called gas chromatography-mass spectrometry (GC-MS). This will help us create a unique "fingerprint" of the hormones present in the urine of people with mucinous ovarian cancer, as well as those with benign and borderline tumours. 

All participants will also provide samples of fresh ovarian tissue and collect their urine over a 24-hour period. However, only the samples from participants confirmed to have mucinous ovarian cancer will be analysed in detail. They'll be asked to collect all their urine in one container during the 24-hour period and bring it to their next hospital visit, where the clinical team will collect it. 

This part of the study will help us understand more about the specific hormones present in mucinous ovarian cancer and how they might differ from those in other types of ovarian tumours. 

Sub-Study 2 – Follow-Up: 

In the second part of our study, we aim to enrol 50 individuals who have been diagnosed with primary mucinous ovarian cancer through biopsy and have completed their first-line treatment. 

We will analyse the urine samples of these individuals using gas chromatography-mass spectrometry (GC-MS) to understand if there are changes in hormone levels over time, especially during follow-up appointments or if the cancer returns. Urine samples will be collected every three months during clinical visits. 

Additionally, we will collect fresh ovarian tissue and 24-hour urine samples from all participants. They will be asked to collect all their urine in one container during the 24-hour period before their hospital visit, where the clinical team will collect it. 

Pathologists who specialize in gynaecological cancers at the three main sites (University Hospital, City Hospital, and Birmingham Women’s and Children’s Hospital) will carefully review the tissue samples to ensure accurate histological diagnosis. We will then compare the hormone profiles in the urine samples with the histological findings to see if there are any connections between them. 

The data collected will undergo thorough statistical and computational analysis, including descriptive statistics, visualizations using software like SigmaPlot and Prism, and the use of machine learning techniques such as MatLab. If we identify distinct hormone profiles, we will develop and validate a high-throughput urine assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to save time in future analyses. 

This part of the study will help us understand how hormone levels change over time in mucinous ovarian cancer patients and if these changes could be used to monitor the progression of the disease or predict recurrence. 

Sub-Study 3 - Control: 

In the third part of our study, we will look at the hormone levels in urine samples from individuals with mucinous colorectal cancer, along with other types of tumours. 

We plan to recruit a total of 25 individuals for this part of the study. We will collect urine samples from all participants over a 24-hour period, using a technique called gas chromatography-mass spectrometry (GC-MS) to analyse the hormone levels in the urine. This will help us create a unique "fingerprint" of the hormones present in the urine of people with mucinous colorectal cancer, as well as those with ovarian tumours. 

Participants will be asked to collect all their urine in one container during the 24-hour period before their hospital visit, where the clinical team will collect it. 

By comparing the hormone profiles in the urine samples from individuals with different types of tumours, we hope to better understand how hormone levels might differ between mucinous colorectal cancer and other types of tumours. This could provide valuable insights into the underlying biology of these cancers and potentially lead to new ways of diagnosing or treating them. 

If you would like to learn more about our project or are interested in participating in the future, please contact:

Alex St. John, Study Coordinator at A.j.h.stjohn@bham.ac.uk

Or Professor Sudha Sundar, Principal Investigator at s.s.sundar@bham.ac.uk

Publications

• Beevors LI, Sundar S, Foster PA. Steroid metabolism and hormonal dynamics in normal and malignant ovaries. Essays in Biochemistry. Published online July 12, 2024:EBC20240028. doi:10.1042/EBC20240028
• Olaoye T, Boyle W, Williams A, Ganesan R, Subba K, Goyal A, Leung E, Chowdhary R, Pascoe J, Williams S, Yap J, Balega J, Kumar S, Singh K, Sundar S. Investigating age and ethnicity as novel high-risk phenotypes in mucinous ovarian cancer: retrospective study in a multi-ethnic population. International Journal of Gynecologic Cancer. 2024 Jun 11:ijgc-2024.
• Olaoye T, Subba K, Ganesan R, Williams A, Boyle W, Balega J, Yap J, Singh K, Sundar S. 2022-RA-893-ESGO Is ethnicity a risk factor for differential outcomes in mucinous ovarian cancer? experience from a UK gynaecological oncology centre.

For more information on other mucinous ovarian cancer research, take a look at the link.