A robust negative association between estimated tumour circadian clock function and survival in early stage breast cancer
Vasilyev, V.; Vlachou, D.; Giacchetti, S.; Bjarnason, G. A.; Martino, T. A.; Levi, F.; Dallmann, R.; Rand, D. A.
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Recent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of chronic conditions including cardio-metabolic diseases and cancer. For the latter, they also suggest that chronotherapy offers the potential to refine current treatments and improve the development of future anti-cancer medicines. Therefore, there is a need for tools to measure the functional state of the tumoural circadian clock in patients. We have previously developed a model-led machine-learning algorithm called TimeTeller which has the potential to provide such a tool. Here we demonstrate its potential for clinical relevance by a study of 1286 breast cancer patients in which we characterise the nature of the circadian clock disruption in their tumours and demonstrate a strong nonlinear association between 10-year survival and TimeTellers tumoural clock disfunction score {Theta}. We find that good tumour clock function is antagonistic to survival.
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