Zhao Chifeng, Zhu Haoran, Tian Yu, Sun Yuewen, Zhang Zhenxing
Department of Stomatology, Taizhou Central Hospital (Taizhou University Hospital), No.999, Donghai Avenue, Taizhou, 318000, Zhejiang, People's Republic of China.
Health Science Center, Xi'an Jiaotong University, Xi'an, 710000, Shaanxi, China.
Discov Oncol. 2024 Nov 7;15(1):627. doi: 10.1007/s12672-024-01513-z.
Enhanced infiltration of eosinophils is observed surrounding solid tumors. Some studies indicate that Eosinophil extracellular traps (EETs) play a crucial role in tumor progression and metastasis. However, its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study established a gene set associated with eosinophil differentiation, chemotaxis, and EETs release from previous research. Employing bioinformatics techniques, the expression and biological significance of these genes in HNSCC were analyzed. Briefly, unsupervised clustering based on expression patterns of 133 EETs-related genes to classify TCGA-HNSCC patients. Immune cell infiltration patterns were assessed using "ImmuCellAI" package. A prognostic model was constructed using ten algorithms, with EETs-related gene sets as input features. Here, unsupervised clustering of samples into two types revealed worse prognosis for Cluster 1 (C1) patients after the first year. Cluster 2 (C2) exhibited higher ImmuneScore, but with a distinct immune cell infiltration pattern from the C1. Additionally, high eosinophil abundance only in the C2 had a positive prognostic impact. Serine peptidase inhibitor kazal type 5 (SPINK5) emerged as a potential key gene mediating the formation of EETs in HNSCC. EETs not only exhibit a positive correlation with diverse anti-cancer pathways but also demonstrate positive associations with processes such as proliferation, migration, and other critical pathways. The random survival forest (RSF) model was identified as the optimal eosinophil-related prognostic model. Collectively, this study elucidates the potential impact and mediating pathways of EETs on tumors, providing a reference for targeted therapy based on EETs-related genes.
在实体瘤周围观察到嗜酸性粒细胞浸润增强。一些研究表明，嗜酸性粒细胞胞外陷阱（EETs）在肿瘤进展和转移中起关键作用。然而，其在头颈部鳞状细胞癌（HNSCC）中的具体作用仍不清楚。本研究基于先前的研究建立了一个与嗜酸性粒细胞分化、趋化作用和EETs释放相关的基因集。运用生物信息学技术，分析了这些基因在HNSCC中的表达及生物学意义。简而言之，基于133个与EETs相关基因的表达模式进行无监督聚类，对TCGA-HNSCC患者进行分类。使用“ImmuCellAI”软件包评估免疫细胞浸润模式。以与EETs相关的基因集作为输入特征，使用十种算法构建预后模型。在此，将样本无监督聚类为两种类型，结果显示第1组（C1）患者在第一年之后预后较差。第2组（C2）表现出较高的免疫评分，但与C1的免疫细胞浸润模式不同。此外，仅在C2中高嗜酸性粒细胞丰度具有积极的预后影响。丝氨酸蛋白酶抑制剂Kazal型5（SPINK5）成为HNSCC中介导EETs形成的潜在关键基因。EETs不仅与多种抗癌途径呈正相关，而且与增殖、迁移等过程以及其他关键途径也呈正相关。随机生存森林（RSF）模型被确定为最佳的嗜酸性粒细胞相关预后模型。总的来说，本研究阐明了EETs对肿瘤的潜在影响及介导途径，为基于EETs相关基因的靶向治疗提供了参考。
