Dataset Information

Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC), the most common malignancy of the head and neck, has an overall 5-year survival rate of <50%. Genes associated with cuproptosis, a newly identified copper-dependent form of cell death, are aberrantly expressed in various tumours. However, their role in HNSCC remains unknown. In this study, bioinformatic analysis revealed that the cuproptosis-related gene CDKN2A was correlated with the malignant behaviour of HNSCC. Kaplan-Meier (KM) curves showed that patients with high CDKN2A expression had a better prognosis. Multiomic analysis revealed that CDKN2A may be associated with cell cycle and immune cell infiltration in the tumour microenvironment and is important for maintaining systemic homeostasis in the body. Furthermore, molecular docking and molecular dynamics simulations suggested strong binding between plicamycin and CDKN2A. And plicamycin inhibits the progression of HNSCC in cellular assays. In conclusion, this study elucidated a potential mechanism of action of the cuproptosis-associated gene CDKN2A in HNSCC and revealed that plicamycin targets CDKN2A to improve the prognosis of patients.

SUBMITTER: Fan K

PROVIDER: S-EPMC9868476 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma.

Fan Kaihui K Dong Yuke Y Li Tao T Li Yujie Y

Frontiers in genetics 20230109

Head and neck squamous cell carcinoma (HNSCC), the most common malignancy of the head and neck, has an overall 5-year survival rate of <50%. Genes associated with cuproptosis, a newly identified copper-dependent form of cell death, are aberrantly expressed in various tumours. However, their role in HNSCC remains unknown. In this study, bioinformatic analysis revealed that the cuproptosis-related gene CDKN2A was correlated with the malignant behaviour of HNSCC. Kaplan-Meier (KM) curves showed tha ...[more]

PMID: 36699463

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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.

Dataset Information

Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma.

Publications

Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma.

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