Identification of a Novel Cuproptosis-Related Gene Signature for Prognostic Implication in Head and Neck Squamous Carcinomas

Abstract

Head and neck squamous carcinoma (HNSC) is a frequent and deadly malignancy that is challenging to manage. The existing treatment options have considerable efficacy limitations. Hence, the identification of new therapeutic targets and the development of efficacious treatments are urgent needs. Cuproptosis, a non-apoptotic programmed cell death caused by excess copper, has only very recently been discovered. The present study investigated the prognostic importance of genes involved in cuproptosis through the mRNA expression data and related clinical information of HNSC patients downloaded from public databases. Our results revealed that many cuproptosis-related genes were differentially expressed between normal and HNSC tissues in the TCGA cohort. Moreover, 39 differentially expressed genes were associated with the prognosis of HNSC patients. Then, a 24-gene signature was identified in the TCGA cohort utilizing the LASSO Cox regression model. HNSC expression data used for validation were obtained from the GEO database. Consequently, we divided patients into high- and low-risk groups based on the 24-gene signature. Furthermore, we demonstrated that the high-risk group had a worse prognosis when compared to the low-risk group. Additionally, significant differences were found between the two groups in metabolic pathways, immune microenvironment, etc. In conclusion, we found a cuproptosis-related gene signature that can be used effectively to predict OS in HNSC patients. Thus, targeting cuproptosis might be an alternative and promising strategy for HNSC patients.

Cuproptosis-Related lncRNA Gene Signature Establishes a Prognostic Model of Gastric Adenocarcinoma and Evaluate the Effect of Antineoplastic Drugs

“…We started by comparing the expression of a group of DEGs, or differentially expressed genes, in the two groups. We used the following rules by referring to previous studies [ 8 , 16 ]: if the LogFC (fold change) is greater than 1 or less than −1 (|logFC| > 1), we think that the gene is expressed significantly differently in the two risk groups. Furthermore, the FDR (false discovery rate) should less than 0.05.…”

Identification of a novel cuproptosis‐related gene signature for rheumatoid arthritis—A prospective study

“…Cuproptosis is identified as a novel modality of mitochondrial cell death induced by dysregulation of copper homeostasis. Accumulating bioinformatic studies have indicated the involvement of cuproptosis in the immune infiltration of various malignancies such as pancreatic cancer, 7 gastric cancer, 8 lung adenocarcinoma, 9 renal cell carcinoma, 10 head and neck squamous carcinomas, 11 gliomas, 12 cutaneous melanoma, 13,14 cervical cancer 15 and endometrial carcinoma 16 . Cell death disorder has been identified to play an important part in the pathogenesis of RA.…”

Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma

“…Intratumor copper can regulate the expression of PD-L1, affect the immune escape of tumours, and then affect the efficacy of immunotherapy [ 111 ]. Mutations in the mitochondrial ribosomal gene MRPS7 affect mitochondrial respiratory chain dysfunction, and high expression of MRPS7 is associated with poor prognosis in patients with HNSCC [ 112 , 113 ]. Studies have shown that high-dose Cu2 + exposure induces oxidative stress by increasing the levels of ROS and protein carbonyl compounds and reducing the GSH content and mRNA and enzyme activities, resulting in mitochondrial membrane potential depolarization, Cyto C release, cleavage of caspase-9 and caspase-3, increased BAK and BAX levels, decreased BCL2 levels and induction of tumour cell apoptosis [ 114 ].…”