Disruptions in circadian rhythms and nicotinamide metabolism caused by chemoradiotherapy are associated with behavioral toxicities in esophageal cancer
This study aimed to explore the systemic molecular mechanisms underlying behavioral toxicities, particularly sleep disturbance, in patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive concurrent chemoradiotherapy (dCRT). We performed a prospective, single-center, paired longitudinal study including 30 ESCC patients, with peripheral blood samples collected before treatment (T0) and after treatment (T1). We integrated mRNA-seq transcriptomics and plasma untargeted metabolomics, combined with patient-reported symptom assessments using the MDASI-GI-C scale. Multivariate statistical and multi-omics network analyses were applied to identify key genes, metabolites, and biological pathways associated with treatment-induced symptom worsening. The results revealed that dCRT leads to significant downregulation of core circadian rhythm genes and disruptions in nicotinate/nicotinamide metabolism and retinol metabolism, which are closely linked to exacerbated sleep disturbance and other behavioral toxicities. This transcriptomic dataset provides a comprehensive resource for understanding the systemic molecular alterations underlying chemoradiotherapy-related toxicities in esophageal cancer and supports the development of potential biomarkers and intervention targets.