Circulating 8-Oxo-dG, NUDT1 Expression and Saffron-Metabolite Exposure During Lung-Cancer Therapy: A Prospective Cohort Study
Keywords:
8-oxo-dG, NUDT1, lung cancer, saffron metabolites, oxidative stress, biomarkersAbstract
Background: Treatment-induced oxidative stress varies markedly among patients receiving systemic therapy for lung cancer. Diet-derived antioxidant exposure may contribute to this variability, but mechanistic biomarker data are sparse.
Objective: To characterise longitudinal relationships among circulating 8-oxo-dG, tumour NUDT1 expression, treatment toxicity and measurable saffron-derived metabolites.
Methods: One hundred twenty patients starting first-line systemic therapy were followed for 12 weeks. Plasma 8-oxo-dG and targeted metabolite panels were measured at baseline, week 4 and week 12. Archived tumour tissue was scored for NUDT1 expression. Dietary exposure was recorded using repeated short food-frequency assessments. Mixed-effects models adjusted for treatment class, smoking, age and baseline disease burden.
Results: Plasma 8-oxo-dG rose during the first treatment cycle and partially normalised by week 12. High tumour NUDT1 expression was associated with a smaller early increase in circulating 8-oxo-dG but greater cumulative treatment resistance in exploratory analyses. Detectable crocetin-related metabolites were present in 19% of participants and were associated with lower week-4 C-reactive protein after adjustment, although the confidence interval was wide. No significant association was observed between metabolite detection and radiological response. Patients in the highest oxidative-stress trajectory had more grade ≥2 fatigue and mucositis.
Conclusion: Longitudinal oxidative-stress profiles may capture clinically relevant heterogeneity during lung-cancer therapy. The observed association between saffron-related metabolite exposure and inflammation is exploratory and should not be interpreted causally, but it supports controlled pharmacokinetic and intervention studies that integrate diet, redox biology and tumour NUDT1 status.
Publication format: research abstract. No full-text manuscript accompanies this record.
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Copyright (c) 2026 Gabriel Oliveira, Ethan Clarke, Ayaan Qureshi
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