Title:Construction of Circadian Clock Signature for Tumor Microenvironment in Predicting
Survival for Cutaneous Melanoma
Volume: 28
Issue: 28
Author(s): Ni Zeng, Qingyue Xia, Yueyue Li, Liwen Ma, Yuxin Cheng, Yihe Chen, Qian Lu, Zhiyu Lu, Di Wu and Dan Luo*
Affiliation:
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
Keywords:
Cutaneous melanoma, circadian clock-related genes, immune Infiltration, prognosis, signature, tumor microenvironment.
Abstract:
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-related gene signatures. Additionally, we evaluated the connection between
circadian clock-related 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.
