Acircadian rhythm-related gene signature for predicting survival and drug response in HNSC

Abstract

Head and neck squamous cell carcinoma (HNSC) represents one of the most common malignant carcinomas worldwide. Because the 5-year survival rate of patients with HNSC is poor, it is necessary to develop an effective signature for predicting the risk of HNSC. To identify a circadian rhythm (CR)-related predictive signature, we analyzed the RNA-seq data of patients with HNSC from The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Nine CR-related genes (PER2, PER3, GHRL, CSF2, HDAC3, KLF10, PRKAA2, PTGDS, and RORB) were identified to develop a CR-related signature. The area under the curve values for 5-year overall survival were 0.681, 0.700, and 0.729 in the training set, validation set, and an external independent test set (GSE41613), respectively. The Kaplan‒Meier curve analysis showed that the high-risk group had a reduced relapse-free survival compared with the low-risk group in the training set, validation set, and test set (P < 0.05). Finally, we observed that the CR-related gene signature was associated with the tumor immune microenvironment, somatic nucleotide variation, and drug response in HNSC. In conclusion, we developed a circadian rhythm-related gene signature for predicting overall survival in HNSC.

Keywords: circadian rhythm; drug response; gene signature; head and neck squamous cell carcinoma; prognosis.