Identification of Pyroptosis-related Gene Prognostic Signature in Head and Neck Squamous Cell Carcinoma

Overview

Journal Cancer Med

Specialty Oncology

Date 2022 May 16

PMID 35574984

Authors

Zhanzhan Li

Lin Shen

Yanyan Li

Liangfang Shen

Na Li

Affiliations

Soon will be listed here.

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is a life-threatening disease with poor prognosis. Pyroptosis has been recently disclosed as a programmed cell death triggered by invasive infection, involved in cancer development. However, the prognosis role of pyroptosis-related genes in HNSCC has not been discussed.

Methods: The RNA sequence data of pyroptosis-related genes were obtained from The Cancer Genome Atlas (TCGA) database. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were performed to screen the HNSCC survival-related signature genes. We established a HNSCC risk model with the identified prognostic genes, then divided the HNSCC patients into low- and high-risk subgroups according to median risk score. Moreover, we utilized Gene Expression Omnibus (GEO) dataset to validate the risk model. Go and KEGG analyses were conducted to reveal the potential function of differential expression of genes that identified between low- and high-risk subgroups. ESTIMATE algorithm was performed to investigate the immune infiltration of tumors. Correlation between signature gene expression and drug-sensitivity was disclosed by Spearman's analysis.

Results: We constructed a HNSCC risk model with identified seven pyroptosis-related genes (CASP1, GSDME, IL6, NLRP1, NLRP2, NLRP6, and NOD2) as prognostic signature genes. High-risk subgroup of HNSCC patients in TCGA cohort correlated with lower survival probability than patients from low-risk subgroup (p < .001), and the result is verified with GEO dataset. In addition, 161 genes were identified differentially expressed between the low- and high-risk subgroups in the TCGA cohort, mainly related to immune response. Higher PD-L1 expression level was found in the high-risk subgroup that indicated the possible employment of immune checkpoint inhibitors. IL6 was positively correlated with WZ3105 and MPS-1-IN-1 in the cancer therapeutics response portal database.

Conclusion: We built and verified a risk model for HNSCC prognosis using seven pyroptosis-related signature genes, which could predict the overall survival of HNSCC patients and facilitate treatment.

Citing Articles

Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC.

Luo X, Li C, Qin G Hereditas. 2025; 162(1):17.

PMID: 39910672 PMC: 11800565. DOI: 10.1186/s41065-025-00380-0.

Comprehensive analyses reveal the promising value of gasdermins as prognostic biomarkers and immunotherapeutic targets in head and neck squamous cell carcinoma.

Huang H, Ge J, Lu S, Deng X, Tian Y, Huang H Heliyon. 2025; 11(1):e41213.

PMID: 39807507 PMC: 11728984. DOI: 10.1016/j.heliyon.2024.e41213.

Prognostic and chemotherapeutic implications of a novel four-gene pyroptosis model in head and neck squamous cell carcinoma.

Yuan P, Jiang S, Wang Q, Wu Y, Jiang Y, Xu H PeerJ. 2024; 12:e17296.

PMID: 38756442 PMC: 11097961. DOI: 10.7717/peerj.17296.

Metabolism-associated molecular classification and prognosis signature of head and neck squamous cell carcinoma.

Jiang M, Gu X, Xu Y, Wang J Heliyon. 2024; 10(6):e27587.

PMID: 38501009 PMC: 10945276. DOI: 10.1016/j.heliyon.2024.e27587.

The proteomics analysis of extracellular vesicles revealed the possible function of heat shock protein 60 in Helicobacter pylori infection.

Li Y, Cao H, Qiu D, Wang N, Wang Y, Wen T Cancer Cell Int. 2023; 23(1):272.

PMID: 37974232 PMC: 10652618. DOI: 10.1186/s12935-023-03131-1.

References

Wang Q, Wang C, Chen J . NLRP6, decreased in gastric cancer, suppresses tumorigenicity of gastric cancer cells. Cancer Manag Res. 2018; 10:6431-6444. PMC: 6267737. DOI: 10.2147/CMAR.S182980. View

Zhou C, Fang J . The role of pyroptosis in gastrointestinal cancer and immune responses to intestinal microbial infection. Biochim Biophys Acta Rev Cancer. 2019; 1872(1):1-10. DOI: 10.1016/j.bbcan.2019.05.001. View

Ju A, Tang J, Chen S, Fu Y, Luo Y . Pyroptosis-Related Gene Signatures Can Robustly Diagnose Skin Cutaneous Melanoma and Predict the Prognosis. Front Oncol. 2021; 11:709077. PMC: 8313829. DOI: 10.3389/fonc.2021.709077. View

Wang L, Qin X, Liang J, Ge P . Induction of Pyroptosis: A Promising Strategy for Cancer Treatment. Front Oncol. 2021; 11:635774. PMC: 7953901. DOI: 10.3389/fonc.2021.635774. View

Williams T, Leeth R, Rothschild D, Coutermarsh-Ott S, McDaniel D, Simmons A . The NLRP1 inflammasome attenuates colitis and colitis-associated tumorigenesis. J Immunol. 2015; 194(7):3369-80. PMC: 4369420. DOI: 10.4049/jimmunol.1402098. View

Kansy B, Concha-Benavente F, Srivastava R, Jie H, Shayan G, Lei Y . PD-1 Status in CD8 T Cells Associates with Survival and Anti-PD-1 Therapeutic Outcomes in Head and Neck Cancer. Cancer Res. 2017; 77(22):6353-6364. PMC: 5690836. DOI: 10.1158/0008-5472.CAN-16-3167. View

Ibrahim J, De Schutter E, De Beeck K . GSDME: A Potential Ally in Cancer Detection and Treatment. Trends Cancer. 2021; 7(5):392-394. DOI: 10.1016/j.trecan.2020.12.002. View

He W, Wan H, Hu L, Chen P, Wang X, Huang Z . Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res. 2015; 25(12):1285-98. PMC: 4670995. DOI: 10.1038/cr.2015.139. View

Zhang M, Gao W, Liu S, Siu S, Yin M, Ng J . CD38 triggers inflammasome-mediated pyroptotic cell death in head and neck squamous cell carcinoma. Am J Cancer Res. 2020; 10(9):2895-2908. PMC: 7539785. View

10.

Reina-Campos M, Scharping N, Goldrath A . CD8 T cell metabolism in infection and cancer. Nat Rev Immunol. 2021; 21(11):718-738. PMC: 8806153. DOI: 10.1038/s41577-021-00537-8. View

11.

Ramsay I, Ma S, Fisher M, Loewy R, Ragland J, Niendam T . Model selection and prediction of outcomes in recent onset schizophrenia patients who undergo cognitive training. Schizophr Res Cogn. 2017; 11:1-5. PMC: 5684434. DOI: 10.1016/j.scog.2017.10.001. View

12.

Wei Y, Huang H, Qiu Z, Li H, Tan J, Ren G . NLRP1 Overexpression Is Correlated with the Tumorigenesis and Proliferation of Human Breast Tumor. Biomed Res Int. 2017; 2017:4938473. PMC: 5682047. DOI: 10.1155/2017/4938473. View

13.

Ye Y, Dai Q, Qi H . A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer. Cell Death Discov. 2021; 7(1):71. PMC: 8026591. DOI: 10.1038/s41420-021-00451-x. View

14.

Cai J, Yi M, Tan Y, Li X, Li G, Zeng Z . Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ. J Exp Clin Cancer Res. 2021; 40(1):190. PMC: 8188724. DOI: 10.1186/s13046-021-01995-7. View

15.

Wang X, Wu X, Wang Q, Zhang Y, Wang C, Chen J . NLRP6 suppresses gastric cancer growth via GRP78 ubiquitination. Exp Cell Res. 2020; 395(1):112177. DOI: 10.1016/j.yexcr.2020.112177. View

16.

Xia X, Wang X, Cheng Z, Qin W, Lei L, Jiang J . The role of pyroptosis in cancer: pro-cancer or pro-"host"?. Cell Death Dis. 2019; 10(9):650. PMC: 6733901. DOI: 10.1038/s41419-019-1883-8. View

17.

Solomon B, Young R, Rischin D . Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments. Semin Cancer Biol. 2018; 52(Pt 2):228-240. DOI: 10.1016/j.semcancer.2018.01.008. View

18.

Shi C, Pamer E . Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011; 11(11):762-74. PMC: 3947780. DOI: 10.1038/nri3070. View

19.

Yunna C, Mengru H, Lei W, Weidong C . Macrophage M1/M2 polarization. Eur J Pharmacol. 2020; 877:173090. DOI: 10.1016/j.ejphar.2020.173090. View

20.

Chavarria-Smith J, Vance R . The NLRP1 inflammasomes. Immunol Rev. 2015; 265(1):22-34. DOI: 10.1111/imr.12283. View