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Circulating biomarkers as prognostic and predictive markers in rectal cancer

Georgiades, Panayiotis 2019. Circulating biomarkers as prognostic and predictive markers in rectal cancer. PhD Thesis, Cardiff University.
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Standard treatment for patients with locally advanced rectal cancer (LARC) is currently preoperative radiotherapy with or without concurrent chemotherapy followed by total mesorectal excision. Approximately 10-20% of patients who receive preoperative therapy currently achieve a complete pathological or clinical response to therapy (pCR and cCR respectively). These patients have been demonstrated to have improved long-term outcomes, such as disease-free survival. At present, there are no methods available to reliably predict which patients will achieve pCR or cCR before surgical intervention or clinical examination respectively. This thesis aims to explore the technical aspects relating to a range of circulating biomarkers that might be used to facilitate this understanding for future evaluation in larger data sets. As part of this thesis, we developed an assay for the extraction and analysis of exosomederived microRNA (exoRNA) in patients with LARC. Using this assay, we detected variable levels of Mir-31, Mir-99a* and Mir-125b in longitudinal plasma samples. No significant associations were observed between microRNA levels and patient clinical outcomes. Circulating tumour DNA (ctDNA) detection in longitudinal plasma samples was lower than expected. The low rate of detection seen in patients with LARC may have been due to technical limitations. Alternatively, this may be indicative of limited ctDNA shedding in this cohort, bringing into question the potential utility of this biomarker in these patients as a future routine test. We also investigated the ability of immune and derived systemic inflammatory ratios to predict patient response to therapy in an expanded cohort of 235 patients with LARC. Again, few significant findings were observed. Overall, our findings suggest that the use of these circulating biomarkers may have limited clinical efficacy in patients with LARC.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 30 June 2020
Last Modified: 30 Jun 2020 15:35

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