Prognostic and chemotherapeutic implications of a novel four-gene pyroptosis model in head and neck squamous cell carcinoma
Peiyang Yuan,
Sixin Jiang,
Qiuhao Wang,
Yuqi Wu,
Yuchen Jiang,
Hao Xu,
Lu Jiang,
Xiaobo Luo
Affiliations
Peiyang Yuan
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Sixin Jiang
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Qiuhao Wang
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Yuqi Wu
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Yuchen Jiang
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Hao Xu
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Lu Jiang
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Xiaobo Luo
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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 in vitro. 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.
