Huang Huageng, Ge Jingjing, Lu Shunzhen, Deng Xinyi, Tian Ying, Huang He, Wang Zhao, Yao Yuyi, Hong Huangming, Lin Tongyu
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 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.
Heliyon. 2024 Dec 14;11(1):e41213. doi: 10.1016/j.heliyon.2024.e41213. eCollection 2025 Jan 15.
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.
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.
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 ( < 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, = 0.0053) and decreased GSDME expression (HR = 1.42, = 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.
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.
在多项头颈部鳞状细胞癌（HNSC）研究中，已观察到细胞焦亡对肿瘤发生和治疗敏感性的调控作用。然而，作为细胞焦亡决定性执行者的gasdermin家族成员（GSDMs，包括GSDMA/B/C/D/E和PJVK）在HNSC中的系统分析尚未见报道。
基于公开可用数据集的计算方法和生物信息学分析，我们对HNSC中GSDMs的表达谱、预后价值、调控网络和免疫浸润调节进行了全面分析。
共有18.65%（94/504）的HNSC患者存在GSDM改变，最主要的类型是扩增。与正常组织相比，GSDMs的mRNA和蛋白水平，尤其是GSDMD/E，在HNSC中普遍升高（<0.05）。此外，HNSC患者临床病理亚组之间GSDMs的表达存在显著差异。HNSC患者的总生存期受益于GSDMC表达增加（HR = 0.67， = 0.0053）和GSDME表达降低（HR = 1.42， = 0.0140）。调控网络分析揭示了几个与GSDMs相关的重要生物学过程，包括免疫反应中细胞因子产生的正调控。值得注意的是，几乎所有浸润性免疫细胞和免疫检查点都与GSDMA/C/E表达呈负相关，与GSDMB/D和PJVK表达呈正相关。
我们指出了GSDMs（尤其是GSDME）在HNSC发病机制、进展和免疫治疗反应中的潜在作用，为进一步的前瞻性研究和分子机制探索提供了重要证据。
