BackgroundColorectal cancer (CRC) exhibits substantial biological and prognostic heterogeneity that is not fully captured by conventional clinicopathological staging, and the interplay between the cellular senescence and circadian dysregulation in CRC remains insufficiently defined.MethodsWe integrated bulk transcriptomic and clinical data from public CRC cohorts to construct a senescence-circadian interplay score (SCore). Senescence-related and circadian-related gene sets were intersected with CRC differentially expressed genes to identify candidate genes, from which a four-gene random survival forest model was established.
The model was evaluated in the TCGA-COAD/READ training cohort and externally validated in GSE12945 and GSE39582. We further characterized clinicopathological associations, prognostic independence, nomogram performance, pathway enrichment, consensus molecular subtype distribution, immune landscape features, and predicted drug sensitivity.
Single-cell RNA sequencing dataset was used to localize SCore-associated programs and to examine T-cell communication and differentiation dynamics. In addition, RT-qPCR in CRC cell lines, immunohistochemical validation in 120 paired CRC and adjacent non-tumor tissues, and NOX4-centered knockdown experiments were performed to provide orthogonal experimental support.ResultsA higher SCore was consistently associated with poorer overall survival across cohorts and retained prognostic value when integrated with clinicopathological variables.
Frontiers in Immunology published a clinical update in Infectious Disease on 03 Jun 2026.
The item focuses on Senescence-circadian interplay stratifies patient prognosis and reveals immune remodeling heterogeneity in colorectal cancer.
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