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Identification of circulating miRNA biomarkers in thyroid disease

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Project Description

Background: Currently, calcitonin, thyroglobulin and thyroid stimulating hormone receptor antibodies (TSH-R-Ab) can help monitor thyroid cancer post-operatively, however, these cannot distinguish between benign and malignant neoplasms, or between different severity of disease pre-operatively (Xiao et al., 2020; Macvanin et al. 2023). The identification of new biomarkers would not only help in cancer diagnosis, they would also help monitor the progress of disease in patients with microcarcinomas, where diagnosis often leads to over treatment (Zaridze et al., 2021; Sugitani et al., 2021). Similarly, TSH-R-Ab are used to monitor Graves’ disease, but further biomarkers which might identify patients likely to develop severe eye disease would help in the management of the disease (Zhang et al., 2018).

Aim: To determine differences in expression of a focussed panel of miRNA in the serum of patients with benign thyroid disease and thyroid carcinoma compared to healthy individuals.

Preliminary work: Thyroid tissue (benign [non-Graves’], Graves’ and carcinoma), have been incubated in a tissue-on-chip device allowing the collection of tissue-derived small extracellular vesicles (sEV). The microRNA (miR) from these sEV has been extracted and sequenced. Significant up-regulation of miR-375-3p, miR-7-5p, miR-382-5p, and miR-127-3p was observed in sEV from Graves’ tissue compared to those from other benign tissue. Similarly, miR-375-3p and miR-7-5p were also significantly up-regulated in sEV from Graves’ tissue compared to sEV from cancer tissue. No difference was observed between cancer and benign sEV. qRT-PCR validation similarly found elevated levels of miR-375-3p and miR-382-5p in Graves’ tissue sEV compared to benign tissue sEV but this difference was not significant. In contrast to the sequencing data, miR-375-3p, miR-382-5p, and miR-127-3p were all up-regulated in cancer sEV compared to benign sEV (Haigh et al., 2023). The plan for the current study is to utilise this preliminary data to determine whether differences in expression of these miRs and others which tended towards significance, can also be detected in patient’s serum compared to those from healthy individuals. The serum has already been collected from 26 patients and the remaining samples will be collected over the first 6 months of the project, based on previous recruitment.
Objective: To use qRT-PCR to measure the levels of previously identified miRNA of interest in sEV isolated from serum of healthy individuals (n=15), patients with benign thyroid disease, including Graves’ (n=15) and patients with thyroid carcinoma (n=15).

sEV will be isolated by ultracentrifugation from all serum samples (Thery et al., 2016) and RNA extracted using the QIAGEN miRNeasy microkit. qRT-PCR will be used to quantify the levels of a panel of up to 10 miRNA (including miR-375-3p, miR-7-5p, miR-382-5p, and miR-127-3p) that were found to be of interest using the previous sequencing data. Comparison between the different thyroid pathologies will be achieved using the GeneGlobe analysis tool following normalisation against stable miR using geNorm (Qiagen). This will identify potential miRNA biomarkers which will then be evaluated in a larger, multi-centre study.

Status Project Live
Funder(s) British Association of Endocrine & Thyroid Surgeons
Value £5,000.00
Project Dates Jul 1, 2024 - Jun 30, 2025
This project contributes to the following UN Sustainable Development Goals
SDG 3 - Good Health and Well-Being

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