Novel biomarkers in recurrent differentiated thyroid cancer

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Nieto 2020, Hannah (2020). Novel biomarkers in recurrent differentiated thyroid cancer. University of Birmingham. Ph.D.

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Abstract

Thyroid cancer is increasing in incidence worldwide and while outcomes are generally good, up to 25% of patients have tumours which recur after treatment, with a significant impact on their quality of life and life expectancy. The hypothesis of this PhD was that thyroid tumours which subsequently recur display a distinct pattern of driver mutations, or RNA and microRNA expression patterns to those that do not, and that the molecular characterisation of these alterations will reveal novel mechanisms involved in thyroid tumour recurrence. Controlled access TCGA data on thyroid cancer were downloaded and a bioinformatic whole exome sequencing analysis was performed on 43 recurrent patients. This identified mutations in genes including IMPDH2, PFKFB4 and DICER1. A differential expression analysis of RNA and microRNA compared recurrent (n=43) to non-recurrent (n=457) TCGA patients. In the RNA analysis genes involved in matrix adhesion and thyroid cancer pathogenesis were most differentially expressed in recurrent patients, including fibronectin 1 (FN1), α3 integrin (ITGA3) and the proto-oncogene MET. MicroRNA analysis highlighted miR 221, 486 and 1179 as significantly differentially expressed miRs in cancer recurrence. Functional in vitro analysis of demonstrated potential functional roles for the candidate genes highlighted by the RNA and microRNA analysis. This suggests that altered RNA and miRNA expression levels may be key to predicting thyroid cancer recurrence.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):