Identification of exosomal miRNA biomarkers in thyroid disease using microfluidics

Project Description

Invasive tissue biopsies remain the gold standard for diagnosis of diseases within solid tissues. However, for some diseases, accessibility of the tissue prevents a diagnostic biopsy and for those that are sampled, the biopsy only takes a small fraction of what is known to be a highly heterogeneous mix of cells. In addition, diseases constantly evolve, meaning that a biopsy taken at the start of treatment may not represent the tissue throughout or post treatment. The identification of specific biomarkers, which could be detected in biofluids, using minimally invasive techniques, would allow faster diagnosis and easier monitoring of disease, improving the evidence base for clinical decision-making. This application focusses on thyroid diseases, where, in the case of thyroid cancer, its’ increasing prevalence justifies the need for the identification of less invasive more accurate biomarkers.

Specific thyroid biomarkers, including thyroglobulin and calcitonin, are used as surrogate markers of thyroid cancer activity following treatment and recurrence, but limitations with sensitivity and specificity are apparent. In addition, the over treatment of microcarcinomas could be circumvented if biomarker monitoring informed the clinician when, and if, intervention is required.

Graves’ disease (GD) is another disorder of the thyroid leading to hyperthyroidism and is characterized by elevated antibodies to the thyrotropin receptor (TSH-R-Ab). Up to 5% of patients with GD go on to develop severe orbitopathy (GO) which can lead to blindness. Although, high TSH-R-Ab helps identify such patients, additional biomarkers for both GD and GO would increase accuracy and help develop personalized treatment plans.

MicroRNAs (miRNA) are small (17-25 nucleotides) non-coding RNA, whose primary role is gene regulation. miRNA have the potential to be biomarkers, as they are present in bodily fluids, either bound to proteins or encapsulated in extracellular vesicles (EV)5. Exosomes are “small” EV (<150nm), released from all cells and contain proteins, miRNA, RNA and DNA. EV are elevated in the blood of patients with thyroid cancer6 and Graves’ disease.

The current proposal will strengthen the collaborations with scientists in the Biomedical Sciences Department (Professor John Greenman and Dr Victoria Green) at the University of Hull and will use established microfluidic technology, developed therein, to maintain thyroid tissue (LREC 15/NE/0412 North East- Newcastle & North Tyneside), in a viable state via continuous perfusion whilst collecting secretions.