Background : Modified nucleosides reflect nucleic acids turnover, and are eliminated into the urine. They can serve as non-invasive biomarkers for monitoring tumour dynamics, and treatment responses. Methods : 8 modified nucleosides were determined by LC-HRMS in urine voids collected in three linical trials recorded on NCT01693848, NCT01693861 and NCT01693835 by a total of 39 patients. The patients’ circadian timing system was studied by wrist actimetry. Rhythms parameters were estimated using Hidden Markov model (HMM) for telemetric activity data and cosinor analysis for urinary nucleosides excretion. Results : Pseudouridine, was ~ 10-fold larger than those of 1-methylguanosine, 1-methyladenosine, or 4-acetylcytidine, and ~100 fold larger than those of adenosine and cytidine. In St 1, a significant increase in the overnight urinary excretion of 1-methylguanosine was associated with prolonged 4-year survival in patients with R1 resection for liver metastases. In St 2, a significant increase in one nucleoside excretion after chemotherapy was associated with that in plasma carcinoembryonic antigen 1-2 months later, and poor survival. In St3, ten fractionated urines were collected over 2-days. Circadian and/or 12-h rhythms were found in up to 48.3% of the patients for pseudouridine. Rhythm amplitudes were significantly associated with rest-activity circadian parameters. Conclusion : Urinary excretion dynamics of modified nucleosides appeared useful for tracking early responses to surgical or medical treatments, and for characterizing circadian control of cellular proliferation in colorectal cancer patients.
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