Abstract
Background: Cuproptosis is a copper-dependent cell death mechanism that is associated with tumor progression, prognosis, and immune response. The potential role of cuproptosis-related genes (CRGs) in the tumor microenvironment in Head and neck squamous cell carcinoma (HNSC) is unclear，and a gene marker is needed to predict clinical outcomes of HNSC.
Patients and methods: In total, 546 HNSC samples were collected from The Cancer Genome Atlas database(TCGA) and 98 samples from Gene Expression Omnibus datasets(GEO).The CRGs were identified in the literature, while the member genes of Signaling by Receptor Tyrosine Kinases(RTKs) pathway were identified by Metascape, Gene-related prognostic models were established and validated in a training set and GEO verification set. Samples were classified using R software packages. A nomogram and calibration curve were constructed to predict patient survival probability to improve the clinical applicability of the genes. Through unsupervised clustering analysis, identified three distinct Cuproptosis Clusters, we further explored the differences of immune cell infiltration, and immunotherapy among the three Clusters.
Results: 4487 differentially expressed genes were identified between 44 adjacent non-tumorous tissues and 502 tumor tissues samples. 11 gene(FLT3, MAP2K2, CDKN2A,PTPRU,IRS2, FGF9,FGFR2,IL6, JUND, FDX1, SHC3)signature was identified.The gene signature used to establish a Prognostic Risk Score,then to construct cases into high- and low-risk groups in terms of overall survival. The 5-year survival AUC in the training and verification sets were 0.693 and 0.642. The corresponding multifactor COX regression analysis found that low-risk group, pathologic N2c, lymphovascular-invasion(NO) and age had clinical independence. The low-risk group has higher ESTIMATEScore and ImmuneScore (P<0.05).
Conclusion: This study revealed the potential effects of CRGs and RTKs gene signature on the TME, clinicopathological features, and prognosis of HNSC，and may offer novel insights into the cancer treatment.