Dataset Information

A novel cuproptosis-related subtypes and gene signature associates with immunophenotype and predicts prognosis accurately in neuroblastoma.

ABSTRACT:

Background

Neuroblastoma (NB) is the most frequent solid tumor in pediatrics, which accounts for roughly 15% of cancer-related mortality in children. NB exhibited genetic, morphologic, and clinical heterogeneity, which limited the efficacy of available therapeutic approaches. Recently, a new term 'cuproptosis' has been used to denote a unique biological process triggered by the action of copper. In this instance, selectively inducing copper death is likely to successfully overcome the limitations of conventional anticancer drugs. However, there is still a gap regarding the role of cuproptosis in cancer, especially in pediatric neuroblastoma.

Methods

We characterized the specific expression of cuproptosis-related genes (CRGs) in NB samples based on publicly available mRNA expression profile data. Consensus clustering and Lasso-Cox regression analysis were applied for CRGs in three independent cohorts. ESTIMATE and Xcell algorithm was utilized to visualize TME score and immune cell subpopulations' relative abundances. Tumor Immune Dysfunction and Exclusion (TIDE) score was used to predict tumor response to immune checkpoint inhibitors. To decipher the underlying mechanism, GSVA was applied to explore enriched pathways associated with cuproptosis signature and Connectivity map (CMap) analysis for drug exploration. Finally, qPCR verified the expression levels of risk-genes in NB cell lines. In addition, PDHA1 was screened and further validated by immunofluorescence in human clinical samples and loss-of-function assays.

Results

We initially classified NB patients according to CRGs and identified two cuproptosis-related subtypes that were associated with prognosis and immunophenotype. After this, a cuproptosis-related prognostic model was constructed and validated by LASSO regression in three independent cohorts. This model can accurately predict prognosis, immune infiltration, and immunotherapy responses. These genes also showed differential expression in various characteristic groups of all three datasets and NB cell lines. Loss-of-function experiments indicated that PDHA1 silencing significantly suppressed the proliferation, migration, and invasion, in turn, promoted cell cycle arrest at the S phase and apoptosis of NB cells.

Conclusions

Taken together, this study may shed light on new research areas for NB patients from the cuproptosis perspective.

SUBMITTER: Tian XM

PROVIDER: S-EPMC9540510 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

A novel cuproptosis-related subtypes and gene signature associates with immunophenotype and predicts prognosis accurately in neuroblastoma.

Tian Xiao-Mao XM Xiang Bin B Yu Yi-Hang YH Li Qi Q Zhang Zhao-Xia ZX Zhanghuang Chenghao C Jin Li-Ming LM Wang Jin-Kui JK Mi Tao T Chen Mei-Lin ML Liu Feng F Wei Guang-Hui GH

Frontiers in immunology 20220923

<h4>Background</h4>Neuroblastoma (NB) is the most frequent solid tumor in pediatrics, which accounts for roughly 15% of cancer-related mortality in children. NB exhibited genetic, morphologic, and clinical heterogeneity, which limited the efficacy of available therapeutic approaches. Recently, a new term 'cuproptosis' has been used to denote a unique biological process triggered by the action of copper. In this instance, selectively inducing copper death is likely to successfully overcome the li ...[more]

PMID: 36211401

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Dataset Information

A novel cuproptosis-related subtypes and gene signature associates with immunophenotype and predicts prognosis accurately in neuroblastoma.

Background

Methods

Results

Conclusions

Publications

A novel cuproptosis-related subtypes and gene signature associates with immunophenotype and predicts prognosis accurately in neuroblastoma.

Similar Datasets

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