Abstract
C-reactive protein (CRP) is an acute-phase plasma protein that can be used as a biomarker for activation of the immune system. A spectral analysis of CRP level over time for patients with gynaecological tumours has been reported by Madondo et al., using a periodogram method, suggesting that there is no significant periodicity in the data. In our study, we investigate the impact of low sample number on periodogram analysis, for non-uniform sampling intervals—we conclude that data of Madondo et al. cannot rule out periodic behaviour. The search for patterns (periodic or otherwise) in the CRP time-series is of interest for providing a cue for the optimal times at which cancer therapies are best administered. In this paper we show (i) there is no evidence to rule out periodicity in CRP levels, and (ii) we provide a prescription for the minimum data sample rate required in future experiments for improved testing of a periodic CRP signal hypothesis. The analysis we provide may be used for establishing periodicity in any short time-series signal that is observed without a priori information.
Highlights
It has been proposed that the immune system exhibits fluctuation in its activity over time and that this can be characterised by oscillation of bio-markers that can measure inflammation, such as acute-phase serum markers and possibly body temperature[1,2]
The authors hypothesised that the C-reactive protein (CRP) oscillations are part of a homeostatic immune response to advanced malignancy from preliminary data linking the timing of therapy to treatment success[1]
Chemotherapy was initiated at the estimated peak of a CRP cycle and it was estimated that all patients exhibited oscillating CRP levels with an average periodicity of 7.8 days[35]
Summary
Mohsen Dorraki 1,2, Anahita Fouladzadeh[3], Stephen J. Chemotherapy was initiated at the estimated peak of a CRP cycle and it was estimated that all patients exhibited oscillating CRP levels with an average periodicity of 7.8 days[35]. They conducted a pilot clinical study of twelve patients with metastatic melanoma who underwent serial CRP measurements every 2–3 days for two weeks Both studies[1,35] highlighted that the timing of either a vaccine-based therapy or cytotoxic chemotherapy relative to specific phases in the immune response cycle of a patient may possibly exert an impact on clinical outcome. In contrast to the previous studies[1,35], Madondo et al.[36] concluded that CRP might not be a convenient bio-marker for the timing of cancer therapies, as their CRP data did not appear to oscillate periodically. We demonstrate use of the Scargle’s significance test for examining the significance of the period obtained from the peak of a periodogram
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