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Peripheral neuropathy (PN) is frequently reported by colorectal cancer (CRC) survivors, and yet the mechanisms remain unclear. Cellular senescence plays a critical role in ageing and ageing-related disorders. Animal studies have found out alleviating senescent cells can alleviate PN. The aim of this study is therefore, to examine the longitudinal associations of cellular senescence-related biomarkers with PN among CRC survivors. To gain insight into the association of senescence-associated biomarkers with PN and pain symptoms, patients with the highest PN scores (HPN, n= 38) and lowest PN scores (LPN, n= 38) from the population-based, prospective cohort PROCORE study were selected. PN was assessed with the EORTC QLQ-CIPN20, and pain symptoms with the EORTC QLQ-C30. Plasma senescence-associated secretory phenotype (SASP) factor (IL-1α, IL-1β, IL-6, IL-8, TGF-α, growth/differentiation factor-15 (GDF-15) and serpin E1 (plasminogen activator inhibitor-1), plasma NAD+ levels, leukocyte telomere length (LTL), leukocyte CD38 and sirtuin activity of each patient were measured at both baseline (ie before cancer treatment) and 2-year follow-up. Patients who reported PN symptoms also had pain complaints, and higher overall SASP factors levels at both baseline and 2-year follow-up. Increased overall sirtuin activity in leukocyte was significantly associated with higher Sensory PN (β: 4.01, 95% CI: 0.39-8.05) and Motor PN scores (β: 3.88, 95% CI: 0.74-7.03) at 2-year follow-up. No associations were observed between all measured biomarkers and pain symptoms.