Construction of Circadian Clock Signature for Tumor Microenvironment in Predicting Survival for Cutaneous Melanoma

Author:

Luo Dan1ORCID,Zeng Ni12ORCID,Xia Qingyue1,Li Yueyue1ORCID,Ma Liwen3,Cheng Yuxin1,Chen Yihe1ORCID,Lu Qian1,Lu Zhiyu1,Wu Di1

Affiliation:

1. Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China

2. Department of Dermatology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Guizhou, 563003, China

3. Department of Dermatology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210000, China

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.

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery,Pharmacology

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