Ultraviolet A (UVA) irradiation can induce cellular senescence and cause skin photoaging, which is mainly driven by excessive production of reactive oxygen species (ROS). Emerging studies have focused on new...
Objective:
We explored circadian clock-related genes (CCRG) to establish a risk model and identify associations with the tumor immune microenvironment in cutaneous melanoma (CM).
Methods:
Circadian clock genes were downloaded from Circadian Gene Database. To explore CM-related circadian clock genes, we combined multivariate cox regression associated with least absolute shrinkage and selection operator (LASSO) regression in the Cancer Genome Atlas (TCGA) and validated it in the GSE65904 dataset. Time-dependent receiver operating characteristic curve (ROC) and Kaplan-Meier analysis were calculated to determine a CCRG risk score model. In addition, the overall survival nomograms of clinicopathological factors and circadian clock-associated gene signatures. Additionally, we evaluated the connection between circadian clock-associated genes with immune checkpoint inhibitors and immune cell infiltration.
Results:
Two circadian-clock-related signatures were established. The risk model included SEMA4D (p < 0.001, HR: 0.709, 95% CI: 0.581 to 0.867) and SOD-2 (p<=0.009, HR: 0.790, 95% CI: 0.663 to 0.944) in patients with TCGA melanoma. The risk model was based on two CCRGs enriched in base excision repair, glycosylphosphatidyl (GPI ), and one carbon of the folate pathway. The overall survival was lower in the high-risk group. In addition, the circadian-clock signature may be able to evaluate the immunotherapy response.
Conclusions:
We developed and validated a circadian signature to characterize the clinical significance and tumor microenvironment of cutaneous melanoma, revealing that circadian rhythms may impact cutaneous melanoma.
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