Comprehensive analyses reveal the promising value of gasdermins as prognostic biomarkers and immunotherapeutic targets in head and neck squamous cell carcinoma
Huageng Huang,
Jingjing Ge,
Shunzhen Lu,
Xinyi Deng,
Ying Tian,
He Huang,
Zhao Wang,
Yuyi Yao,
Huangming Hong,
Tongyu Lin
Affiliations
Huageng Huang
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, PR China
Jingjing Ge
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, PR China
Shunzhen Lu
Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, PR China
Xinyi Deng
Department of Dermatology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, PR China
Ying Tian
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, PR China
He Huang
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, PR China
Zhao Wang
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, PR China
Yuyi Yao
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, PR China
Huangming Hong
Department of Medical Oncology, Senior Ward and Phase I Clinical Trial Ward, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, PR China; Corresponding author. Department of Medical Oncology, Senior Ward and Phase I Clinical Trial Ward, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610000, PR China.
Tongyu Lin
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, PR China; Department of Medical Oncology, Senior Ward and Phase I Clinical Trial Ward, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, PR China
Background: In several studies of head and neck squamous cell carcinoma (HNSC), the regulation of tumorigenesis and therapeutic sensitivity by pyroptosis has been observed. However, a systematic analysis of gasdermin family members (GSDMs, including GSDMA/B/C/D/E and PJVK), which are deterministic executors of pyroptosis, has not yet been reported in HNSC. Methods: We performed comprehensive analyses of the expression profile, prognostic value, regulatory network, and immune infiltration modulation of GSDMs in HNSC on the basis of a computational approach and bioinformatic analysis of publicly available datasets. Results: A total of 18.65 % (94/504) of HNSC patients harbored GSDM alterations, with the most dominant type being amplification. Compared with those in normal tissues, the mRNA and protein levels of GSDMs, especially GSDMD/E, were commonly elevated in HNSC (P < 0.05). Additionally, the expression of GSDMs differed significantly between the clinicopathological subgroups of HNSC patients. Overall survival of HNSC patients benefited from increased GSDMC expression (HR = 0.67, P = 0.0053) and decreased GSDME expression (HR = 1.42, P = 0.0140). Regulatory network analysis revealed several essential biological processes associated with GSDMs, including positive regulation of cytokine production involved in the immune response. Notably, almost all infiltrating immune cells and immune checkpoints were negatively correlated with GSDMA/C/E expression and positively related to GSDMB/D and PJVK expression. Conclusions: We indicated the potential role of GSDMs (especially GSDME) in HNSC pathogenesis, progression and response to immunotherapy, providing important evidence for further prospective studies and molecular mechanism exploration.
