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A pyroptosis-related gene expression signature predicts immune microenvironment and prognosis in head and neck squamous cell carcinoma

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European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive malignancy with a poor prognosis. Pyroptosis triggered by gasdermins family proteins is reported vital for tumor microenvironment and cancer progression. However, pyroptosis-related gene expression and its relationship with immune infiltration and prognosis of HNSCC have not been fully defined.

Material and methods

RNA-sequencing data of HNSCC patients were acquired from The Cancer Genome Atlas (TCGA) database. A pyroptosis-related gene expression signature and infiltrated immune cells were analyzed. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression and nomogram analyses were used to construct a clinical-molecular risk model for survival prognosis.

Results

HNSCC was classified into three different molecular subtypes based on the expression information of pyroptosis-related genes. Immune cell infiltration was demonstrated to be distinct between the three subtypes. The segregation of patients into the high-risk group and low-risk group, were carried out using the signature of differential expression genes (DEGs) signature among the three molecular subtypes. The precision of this signature was corroborated by Receiver operating characteristic curve (ROC) analysis with the 3-year area under time-dependent ROC curve (AUC) reaching 0.711. The risk model was validated in another dataset from the Gene Expression Omnibus (GEO) database. Subsequently we established a clinical-molecular nomogram which combined the risk score with age and stage. The calibration plots for predicting the overall survival rate of 1-, 3-, and 5-years indicated that the nomogram performs well.

Conclusion

The expression signature that encompasses pyroptosis-related genes could be used as molecular classification for HNSCC and pyroptosis might be a promising therapeutic target in HNSCC.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

NMPA:

National Medical Products Administration

HNSCC:

Head and neck squamous cell carcinoma

TCGA:

The Cancer Genome Atlas

LASSO:

Least absolute shrinkage and selection operator

DEGs:

The differentially expression genes

ROC:

Receiver operating characteristic curve

AUC:

Area under time-dependent ROC curve

GEO:

The gene expression omnibus

OS:

Overall survival

GSDM:

Gasdermin

PRRs:

The pattern recognition receptors

NLRPs:

Nucleotide-binding oligomerization domain-like receptor proteins

TME:

Tumor microenvironment

NK:

Natural killer

ICB:

Immune checkpoint blockade

PCA:

The principal component analysis

ssGSEA:

The single sample gene set enrichment analysis

GO:

Gene ontology

KEGG:

Genes and genomes

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Funding

Natural Science Foundation of Fujian Province, 2020J011142, Lina Fan, the Startup Fund for scientific research, University of Chinese Academy of Sciences—Shenzhen Hospital, HRF-2020012, Xuegang Hu, the Guangming District Economic Development Special Fund, 2021R01063, Xuegang Hu, 2021R01065, Long Zhang, Education and Teaching Reform Research Project of Fujian Medical University, J21017, Lina Fan.

Author information

Author notes

  1. Wenyuan Zhou and Mei Feng have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, China

    Wenyuan Zhou

  2. Department of General Surgery, Peking University First Hospital, Beijing, 100034, China

    Mei Feng

  3. Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing, Peking University Cancer Hospital & Institute, Beijing, 100142, China

    Fei Qi

  4. Department of Laboratory Medicine, Peking University Third Hospital, Beijing, 100191, China

    Jiao Qiao

  5. Institute of Medical Technology, Peking University Health Science Center, Beijing, 100191, China

    Jiao Qiao

  6. Department of Stomatology, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, 350025, Fujian, China

    Lina Fan

  7. Department of Stomatology, Shenzhen Guangming District People’s Hospital, Songbai Road 4253, Shenzhen, 518107, Guangdong, China

    Long Zhang & Xuegang Hu

  8. Medical Affairs Department, Shenzhen Guangming District People’s Hospital, Songbai Road 4253, Shenzhen, 518107, Guangdong, China

    Chunyu Huang

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  1. Wenyuan Zhou
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Correspondence to Xuegang Hu or Chunyu Huang.

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Supplementary Information

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405_2023_8316_MOESM1_ESM.pdf

Supplementary Figure S (A-B) Validation of the risk model in GSE41613, (A) K-M survival analysis between high- and low-risk group. (B) ROC analysis of the risk model. (C) The correlation between prognostic gene expression and methylation. (D) The correlation between prognostic gene expression and drug sensitivity. file1 (PDF 1729 KB)

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Zhou, W., Feng, M., Qi, F. et al. A pyroptosis-related gene expression signature predicts immune microenvironment and prognosis in head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 281, 953–963 (2024). https://doi.org/10.1007/s00405-023-08316-y

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