Prognostic and Chemotherapeutic Implications of a Novel Four-gene Pyroptosis Model in Head and Neck Squamous Cell Carcinoma

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2024 May 17

PMID 38756442

Authors

Peiyang Yuan

Sixin Jiang

Qiuhao Wang

Yuqi Wu

Yuchen Jiang

Hao Xu

Lu Jiang

Xiaobo Luo

Affiliations

Soon will be listed here.

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers. Chemotherapy remains one dominant therapeutic strategy, while a substantial proportion of patients may develop chemotherapeutic resistance; therefore, it is particularly significant to identify the patients who could achieve maximum benefits from chemotherapy. Presently, four pyroptosis genes are reported to correlate with the chemotherapeutic response or prognosis of HNSCC, while no study has assessed the combinatorial predicting efficacy of these four genes. Hence, this study aims to evaluate the predictive value of a multi-gene pyroptosis model regarding the prognosis and chemotherapeutic responsiveness in HNSCC.

Methods: By utilizing RNA-sequencing data from The Cancer Genome Atlas database and the Gene Expression Omnibus database, the pyroptosis-related gene score (PRGscore) was computed for each HNSCC sample by performing a Gene Set Variation Analysis (GSVA) based on four genes (Caspase-1, Caspase-3, Gasdermin D, Gasdermin E). The prognostic significance of the PRGscore was assessed through Cox regression and Kaplan-Meier survival analyses. Additionally, chemotherapy sensitivity stratified by high and low PRGscore was examined to determine the potential association between pyroptosis activity and chemosensitivity. Furthermore, chemotherapy sensitivity assays were conducted in HNSCC cell lines .

Results: As a result, our study successfully formulated a PRGscore reflective of pyroptotic activity in HNSCC. Higher PRGscore correlates with worse prognosis. However, patients with higher PRGscore were remarkably more responsive to chemotherapy. In agreement, chemotherapy sensitivity tests on HNSCC cell lines indicated a positive association between overall pyroptosis levels and chemosensitivity to cisplatin and 5-fluorouracil; in addition, patients with higher PRGscore may benefit from the immunotherapy. Overall, our study suggests that HNSCC patients with higher PRGscore, though may have a less favorable prognosis, chemotherapy and immunotherapy may exhibit better benefits in this population.

References

Zhang J, Pan S, Jian C, Hao L, Dong J, Sun Q . Immunostimulatory Properties of Chemotherapy in Breast Cancer: From Immunogenic Modulation Mechanisms to Clinical Practice. Front Immunol. 2022; 12:819405. PMC: 8766762. DOI: 10.3389/fimmu.2021.819405. View

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

Inoue H, Tani K . Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments. Cell Death Differ. 2013; 21(1):39-49. PMC: 3857623. DOI: 10.1038/cdd.2013.84. View

Li Z, Shen L, Li Y, Shen L, Li N . Identification of pyroptosis-related gene prognostic signature in head and neck squamous cell carcinoma. Cancer Med. 2022; 11(24):5129-5144. PMC: 9761089. DOI: 10.1002/cam4.4825. View

Wang S, Zhang M, Wu Z, Zhu S, Wan S, Zhang B . GSDME Is Related to Prognosis and Response to Chemotherapy in Oral Cancer. J Dent Res. 2022; 101(7):848-858. DOI: 10.1177/00220345211073072. View

Liu F, Xing L, Zhang X, Zhang X . A Four-Pseudogene Classifier Identified by Machine Learning Serves as a Novel Prognostic Marker for Survival of Osteosarcoma. Genes (Basel). 2019; 10(6). PMC: 6628621. DOI: 10.3390/genes10060414. View

Yu P, Wang H, Tian M, Li A, Chen X, Wang X . Eukaryotic elongation factor-2 kinase regulates the cross-talk between autophagy and pyroptosis in doxorubicin-treated human melanoma cells in vitro. Acta Pharmacol Sin. 2019; 40(9):1237-1244. PMC: 6786479. DOI: 10.1038/s41401-019-0222-z. View

Lu H, Zhang S, Wu J, Chen M, Cai M, Fu Y . Molecular Targeted Therapies Elicit Concurrent Apoptotic and GSDME-Dependent Pyroptotic Tumor Cell Death. Clin Cancer Res. 2018; 24(23):6066-6077. DOI: 10.1158/1078-0432.CCR-18-1478. View

Deng H, Wei Z, Qiu S, Ye D, Gu S, Shen Y . Pyroptosis patterns and immune infiltrates characterization in head and neck squamous cell carcinoma. J Clin Lab Anal. 2022; 36(4):e24292. PMC: 8993614. DOI: 10.1002/jcla.24292. View

10.

Wang Y, Yin B, Li D, Wang G, Han X, Sun X . GSDME mediates caspase-3-dependent pyroptosis in gastric cancer. Biochem Biophys Res Commun. 2017; 495(1):1418-1425. DOI: 10.1016/j.bbrc.2017.11.156. View

11.

Lou X, Li K, Qian B, Li Y, Zhang D, Cui W . Pyroptosis correlates with tumor immunity and prognosis. Commun Biol. 2022; 5(1):917. PMC: 9448722. DOI: 10.1038/s42003-022-03806-x. View

12.

Rioja-Blanco E, Arroyo-Solera I, Alamo P, Casanova I, Gallardo A, Unzueta U . CXCR4-targeted nanotoxins induce GSDME-dependent pyroptosis in head and neck squamous cell carcinoma. J Exp Clin Cancer Res. 2022; 41(1):49. PMC: 8815235. DOI: 10.1186/s13046-022-02267-8. View

13.

Wang Y, Gao W, Shi X, Ding J, Liu W, He H . Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017; 547(7661):99-103. DOI: 10.1038/nature22393. View

14.

Wang H, Liu F . LSD1 silencing inhibits the proliferation, migration, invasion, and epithelial-to-mesenchymal transition of hypopharyngeal cancer cells by inducing autophagy and pyroptosis. Chin J Physiol. 2023; 66(3):162-170. DOI: 10.4103/cjop.CJOP-D-22-00137. View

15.

Lu L, Zhang P, Cao X, Guan M . Prognosis and Characterization of Immune Microenvironment in Head and Neck Squamous Cell Carcinoma through a Pyroptosis-Related Signature. J Oncol. 2022; 2022:1539659. PMC: 9007648. DOI: 10.1155/2022/1539659. View

16.

Lee E, Chuang H, Kim J, Ideker T, Lee D . Inferring pathway activity toward precise disease classification. PLoS Comput Biol. 2008; 4(11):e1000217. PMC: 2563693. DOI: 10.1371/journal.pcbi.1000217. View

17.

Chen J, Ge L, Shi X, Liu J, Ruan H, Heng D . Lobaplatin Induces Pyroptosis in Cervical Cancer Cells via the Caspase-3/GSDME Pathway. Anticancer Agents Med Chem. 2021; 22(11):2091-2097. DOI: 10.2174/1871520621666211018100532. View

18.

Jia Y, Wang X, Deng Y, Li S, Xu X, Qin Y . Pyroptosis Provides New Strategies for the Treatment of Cancer. J Cancer. 2023; 14(1):140-151. PMC: 9809330. DOI: 10.7150/jca.77965. View

19.

Zhu W, Ye Z, Chen L, Liang H, Cai Q . A pyroptosis-related lncRNA signature predicts prognosis and immune microenvironment in head and neck squamous cell carcinoma. Int Immunopharmacol. 2021; 101(Pt B):108268. DOI: 10.1016/j.intimp.2021.108268. View

20.

Wu M, Wang Y, Yang D, Gong Y, Rao F, Liu R . A PLK1 kinase inhibitor enhances the chemosensitivity of cisplatin by inducing pyroptosis in oesophageal squamous cell carcinoma. EBioMedicine. 2019; 41:244-255. PMC: 6442225. DOI: 10.1016/j.ebiom.2019.02.012. View