Occurrence of microRNAs in the plasma of MEN1 patients and their feasibility as biomarkers

Kate Lines BSc (Hons) PhD

Kate, who works at the Academic Endocrine Unit at the University of Oxford as a Postdoctoral Research Assistant, received a grant of £9,994.

About Kate

After graduating she continued in the field of tumour research by beginning a Molecular Oncology PhD at the Barts Cancer Institute focusing on pancreatic cancer, which she completed in 2011. After this she began her academic research career at the University of Oxford where she continued the theme of tumour research by moving into the field of endocrine tumourigenesis. She has now been part of the Academic Endocrine Unit at the University of Oxford for 18 months where her work primarily involves investigating the role of microRNAs and proteins in the regulation of gene expression, with a focus on the MEN1 gene. So far this research has shown promising results and she aims to continue her academic career in this field.

On being notified and congratulated on her successful application, Kate commented, “I am delighted to receive the 2013 AMEND Research Fund Award for the project ‘Occurrence of microRNAs in the plasma of MEN1 patients and their feasibility as biomarkers’. By receiving this award we will be able to perform initial studies to determine whether microRNAs could be used as biomarkers for MEN1 tumours. If successful, in the long term, we hope that a routine blood test could be developed that detects these microRNAs. This would mean that patients with MEN1 could be screened for tumours by giving a simple blood sample, therefore eliminating the need for frequent radiological screening (scanning)”.

Final Project Report

Patients with MEN1 currently have to undergo frequent CT or MRI scanning in addition to annual blood tests to monitor tumour development. Consequently, the development of a non-invasive, reliable neuroendocrine tumour marker is required. Investigation of non-endocrine tumour types has indicated that different tumours can release a specific pattern of small RNA structures called micro-RNAs (miRNAs) and that these can be detected in the blood. In this study we therefore investigated the potential of miRNAs to be biomarkers for tumours in MEN1 patients. As miRNAs have never previously been investigated in the blood of such patients, we firstly optimised a procedure to isolate miRNAs from frozen blood samples.

With this optimised procedure, we then isolated miRNAs from the blood of four MEN1 patients, two male and two female, with a combination of parathyroid and pancreatic tumours, and from unaffected relatives. We then compared the miRNAs present in the patient and unaffected relative to see if the levels were different. In total we found 117 miRNAs with increased levels and 129 miRNAs with decreased levels in the blood of all the MEN1 patients, compared to the unaffected relatives. Two of the most highly decreased miRNAs in the blood of MEN1 patients have never previously been described. We therefore further confirmed the decrease in these miRNAs in two patient pairs and plan to perform further experiments to determine their role in MEN1 tumours. Overall, our study demonstrates that miRNAs can be detected in the blood of MEN1 patients, and that differences in the levels of specific miRNAs can be detected. This paves the way for larger studies to validate the use of miRNAs as MEN2 tumour biomarkers. Furthermore, our studies have highlighted two, previously unidentified miRNAs which may provide new insights into MEN1 tumour biology.

Kate Lines (13 February 2015)

This project was presented at the Oxford Centre for Diabetes and Metabolism Senior Academic Faculty Friday Seminar Series on 9th May 2014 (title: ‘Occurrence of micro RNAs in the plasma of MEN1 patients and their feasibility as biomarkers’), with submission to other medical meetings in progress.