Identification and characterisation of biomarkers that determine the quality of life in cancer survivors

MicroRNAs (miRNAs) have been well-documented in cancer- and cancer treatment-induced complications, and exercise physiology. Oestrogen has been demonstrated to play an important role in response to exercise. However, whether miRNAs altered by cancer and cancer treatment can be used to monitor exercise progress in rehabilitation programmes and whether oestrogen levels can be a potential biomarker of exercise intensity remain unclear. This study aimed to identify potential miRNAs that could be used to monitor exercise progress in cancer survivors and explore the correlations between oestrogen levels and physiological parameters. Chapter 3 described the expression of a panel of muscle-related (miR-1, miR-133, miR-208, miR-486, miR-499) and inflammation-related (miR-21, miR-126, miR- 146, and miR-155) miRNAs selected by literature review. We found that Luminal A had a greater impact on muscle-related miRNAs, while Luminal B had a greater impact on inflammation-related miRNAs. Surgery, chemotherapy, and combined therapy had a prominent effect on miR-21 and miR-486 compared to endocrine therapy. The expression of miR-133 and miR-486 was significantly impacted by treatment duration and age. Chapter 4 described the impact of a 12-week exercise programme on the quality of life and the expression of selected miRNAs in cancer survivors of the CANReact study. We found a 12-week exercise programme could significantly improve physical well-being, but did not improve participants' fatigue levels. Exercise significantly improved the 6-minute walk distance and muscle strength. MiR-126 significantly increased after 12 weeks of exercise, and ΔmiR-126 was positively correlated with Δmuscle mass% (r = 0.548, p=0.015). Inflammation- and musclerelated miRNAs were interrelated, and the higher the inflammation-related miRNAs, the higher the muscle-related miRNAs. The correlations between physiological parameters and the selected miRNAs were weak. Chapter 5 described the expression of oestradiol levels and the role of oestradiol levels in the response of physiological parameters to exercise in 50 female participants in the CAN-React study. We showed that 44 participants had an oestradiol level below 30 pg/mL, and six (12%) had an oestradiol level of more than 30 pg/mL, with a mean oestradiol level in this cohort of 31.5 pg/mL. The sensitivity of oestradiol in predicting the responsiveness of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) to exercise was 70% and 71.4%, with a specificity of 85.7% and 70%, respectively. When oestradiol was 8.64 and 9.93, the area under curve (AUC) was 0.700 and 0.629 in left- and right-hand grip strength, with a sensitivity of 75% and 70%, and a specificity of 80% and 71.4%, respectively.

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University of Galway

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University of Galway Theses (PhD Theses)