Head and Neck Squamous Cell Carcinoma: Cuproptosis-related Long Non-coding RNAs Predict Prognosis and Immunotherapeutic Response

Abstract

Objective Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis because of high recurrence and metastasis rates and failure of immunotherapy caused by escape of immune cells. The aim of this study was to explore potential biomarkers and precise drug therapies for HNSCC.

Methods We extracted the RNA transcriptome dataset and related clinical data of patients with HNSCC from The Cancer Genome Atlas (TCGA) database to analyze differentially expressed long non-coding RNAs (lncRNAs) in HNSCC. We screened differentially expressed lncRNAs related to cuproptosis among regulatory genes and identified those that best indicated the prognosis of HNSCC univariate Cox (uni-Cox) regression analyses and the least absolute shrinkage and selection operator. We constructed models and evaluated their accuracy in determining high- and low-risk groups using the Kaplan–Meier, receiver operating characteristic curve, and uni-Cox regression and multivariate Cox (multi-Cox) regression analyses. Subsequently, we subjected the high-risk group to gene set variation analysis, principal component analysis, immunoassay, and half-maximal inhibitory concentration prediction. To further improve tumor immunotherapy, we divided the entire sample into cold and hot groups based on cuproptosis-related lncRNAs and analyzed the therapeutic differences. Results Combined with cuproptosis-related genes and by analyzing the HNSCC data from TCGA, we obtained five cuproptosis-related prognostic lncRNAs. The model showed certain reliability. Patients in the high- and low-risk groups had different tumor microenvironments and drug sensitivities. Cuproptosis-related lncRNA expression differed between cold and hot tumors. Further, hot tumors were more sensitive to immunotherapy drugs compared to cold tumors. 

Conclusion This study established and verified the lncRNAs that stratified the prognostic risk related to cuproptosis in HNSCC. The model also predicted immunotherapeutic responses of patients with HNSCC and provided a reference for the individualized treatment of cold and hot tumors.