Dataset Information

Cuproptosis-related gene subtypes predict prognosis in patients with head and neck squamous cell carcinoma.

ABSTRACT:

Background

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. A novel form of copper-dependent and reactive oxygen species (ROS)-dependent cell death, cuproptosis, has been described in many cancers. The roles and potential mechanisms of cuproptosis-related genes (CRGs) are still unclear in HNSCC.

Method

We downloaded TCGA datasets of HNSCC genomic mutations and clinic data from The Cancer Genome Atlas. Based on the Cuproptosis-related differentially expressed genes in HNSCC, we constructed a prognostic signature.

Results

Eight CRGs have been identified as associated with the prognosis of HNSCC. According to Kaplan-Meier analyses, HNSCC with a high Risk Score had a poor prognosis. Furthermore, the AUC of the Risk Score for the 1-, 3-, and 5- year overall survival was respectively, 0.70, 0.71, and 0.68. TCGA data revealed that T cell functions, such as HLA, cytolytic activity, inflammation regulation, co-inhibition, and co-stimulation, differed significantly between members of the low and high groups. The immune checkpoint genes PD-L1, PD-L1, and CTLA-4 were also expressed differently in the two risk groups.

Conclusions

A CRG signature was defined that is associated with the prognosis of patients with HNSCC.

SUBMITTER: Wang C

PROVIDER: S-EPMC10496405 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Cuproptosis-related gene subtypes predict prognosis in patients with head and neck squamous cell carcinoma.

Wang Chi C Zhou Yu Y

Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale 20230912 1

<h4>Background</h4>Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. A novel form of copper-dependent and reactive oxygen species (ROS)-dependent cell death, cuproptosis, has been described in many cancers. The roles and potential mechanisms of cuproptosis-related genes (CRGs) are still unclear in HNSCC.<h4>Method</h4>We downloaded TCGA datasets of HNSCC genomic mutations and clinic data from The Cancer Genome Atlas. Based on the Cuproptosis-related differe ...[more]

PMID: 37697421

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Project description:Background: Cuproptosis is a new type of cell death that induces protein toxic stress and eventually leads to cell death. Hence, regulating cuproptosis in tumor cells is a new therapeutic approach. However, studies on cuproptosis-related long noncoding RNA (lncRNA) in head and neck squamous cell carcinoma (HNSC) have not been found. This study aimed to explore the cuproptosis-related lncRNAs prognostic marker and their relationship to immune microenvironment in HNSC by using bioinformatics methods. Methods: RNA sequencing, genomic mutations, and clinical data of TCGA_HNSC were downloaded from The Cancer Genome Atlas. HNSC patients were randomly assigned to either a training group or a validation cohort. The least absolute shrinkage and selection operator Cox regression and multivariate Cox regression models were used to determine the prognostic model in the training cohort, and its independent prognostic effect was further confirmed in the validation and entire cohorts. Results: Based on previous literature, we collected 19 genes associated with cuproptosis. Afterward, 783 cuproptosis-related lncRNAs were obtained through coexpression. Cox model revealed and constructed eight cuproptosis-related lncRNAs prognostic marker (AL132800.1, AC090587.1, AC079160.1, AC011462.4, AL157888.1, GRHL3-AS1, SNHG16, and AC021148.2). Patients were divided into high- and low-risk groups based on the median risk score. The Kaplan-Meier survival curve revealed that the overall survival between the high- and low-risk groups was statistically significant. The receiver operating characteristic curve and principal component analysis demonstrated the accurate prognostic ability of the model. Univariate and multivariate Cox regression analysis showed that risk score was an independent prognostic factor. In addition, we used multivariate Cox regression to establish a nomogram of the predictive power of prognostic markers. The tumor mutation burden showed significant differences between the high- and low-risk groups. HNSC patients in the high-risk group responded better to immunotherapy than those in the low-risk group. We also found that risk scores were significantly associated with drug sensitivity in HNSC. Conclusion: In summary, our study identified eight cuprotosis-related lncRNAs signature of HNSC as the prognostic predictor, which may be promising biomarkers for predicting the benefit of HNSC immunotherapy as well as drug sensitivity.

Project description:BackgroundThe purpose of this study was to identify the prognostic value of cuproptosis and copper metabolism-related genes, to clarify their molecular and immunological characteristics, and to elucidate their benefits in head and neck squamous cell carcinoma (HNSCC).MethodsThe details of human cuproptosis and copper metabolism-related genes were searched and filtered from the msigdb database and the latest literature. To identify prognostic genes associated with cuproptosis and copper metabolism, we used least absolute shrinkage and selection operator regression, and this coefficient was used to set up a prognostic risk score model. HNSCC samples were divided into two groups according to the median risk. Afterwards, the function and immune characteristics of these genes in HNSCC were analyzed.ResultsThe 14-gene signature was constructed to classify HNSCC patients into low-risk and high-risk groups according to the risk level. In the The Cancer Genome Atlas (TCGA) cohort, the overall survival (OS) rate of the high-risk group was lower than that of the low-risk group (P < 0.0001). The area under the curve of the time-dependent Receiver Operator Characteristic (ROC) curve assessed the good performance of the genetic signature in predicting OS and showed similar performance in the external validation cohort. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment assays and Protein-Protein Interaction (PPI) protein networks have been used to explore signaling pathways and potential mechanisms that were markedly active in patients with HNSCC. Furthermore, the 14 cuproptosis and copper metabolism-related genes were significantly correlated with the immune microenvironment, suggesting that these genes may be linked with the immune regulation and development of HNSCC.ConclusionsOur results emphasize the significance of cuproptosis and copper metabolism as a predictive biomarker for HNSCC, and its expression levels seem to be correlated with immune- related features; thus, they may be a possible biomarker for HNSCC prognosis.

Project description:BackgroundChromatin regulators (CRs) serve as indispensable factors in tumor biological processes by influencing tumorigenesis and the immune microenvironment and have been identified in head and neck squamous cell carcinoma (HNSCC). Hence, CR-related genes (CRRGs) are considered potential biomarkers for predicting prognosis and immune infiltration in HNSCC. In this study, we established a novel signature for predicting the prognosis and immunotherapeutic response of HSNCC.MethodsA total of 870 CRRGs were obtained according to previous studies. Subsequently, patients in the TCGA-HNSC cohort were divided into different clusters based on the expression of prognostic CRRGs. Kaplan‒Meier (K‒M) survival analysis was conducted to compare the prognosis in clusters, and the CIBERSORT and ssGSEA methods assessed the immune infiltration status. In addition, the differences in immunotherapeutic responses were determined based on the TICA database. Furthermore, the differentially expressed CRRGs between clusters were identified, and the predictive signature was established according to the results of univariate Cox, least absolute shrinkage and selection operator regression analysis, and multivariate Cox. The predictive effects of the risk model were evaluated according to the area under the receiver operating characteristic (ROC) curve (AUC) in both the training and external test cohorts. A nomogram was established, and survival comparisons, functional enrichment analyses, and immune infiltration status and clinical treatment assessments were performed. In addition, the hub gene network and related analysis were conducted with the Cytohubba application.ResultsBased on the expression of prognostic CRRGs, patients were divided into two clusters, in which Cluster 1 exhibited a better prognosis, more enriched immune infiltration, and a better immunotherapeutic response but exhibited chemotherapy sensitivity. The AUC values of the 1-, 3- and 5- year ROC curves for the risk model were 0.673, 0.732, and 0.692, respectively, as well as 0.645, 0.608, and 0.623 for the test set. In addition, patients in the low-risk group exhibited more immune cell enrichment and immune function activation, as well as a better immunotherapy response. The hub gene network indicated ACTN2 as the core gene differentially expressed between the two risk groups.ConclusionWe identified molecular subtypes and established a novel predictive signature based on CRRGs. This effective CRRS system can possibly provide a novel research direction for exploring the correlation between CRs and HNSCC and requires further experimental validation.

Dataset Information

Cuproptosis-related gene subtypes predict prognosis in patients with head and neck squamous cell carcinoma.

Background

Method

Results

Conclusions

Publications

Cuproptosis-related gene subtypes predict prognosis in patients with head and neck squamous cell carcinoma.

Similar Datasets

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