Sun Ningjie, Jiang Junjie, Chen Biying, Chen Yiran, Wu Haiming, Wang Haiyong, Chen Jianfeng
Department of Gastrointestinal Surgery, Yiwu Central Hospital, Yiwu, China.
Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
Heliyon. 2024 Sep 3;10(17):e37357. doi: 10.1016/j.heliyon.2024.e37357. eCollection 2024 Sep 15.
Neutrophil extracellular trap (NET) is associated with host response, tumorigenesis, and immune dysfunction. However, the link between NET and the tumor microenvironment (TME) of gastric cancer (GC) remains unclear. Our study aims to characterize the expression patterns of NET-related genes and their relationships with clinicopathological characteristics, prognosis, TME features, and immunotherapy efficacy in GC cohorts.
Transcriptomic and single-cell RNA sequencing profiles of GC with annotated clinicopathological data were obtained from TCGA-STAD (n = 415), GSE62254 (n = 300), GSE15459 (n = 192), and GSE183904 (n = 26). The consensus cluster algorithm was used to classify tumor samples into different NET-related clusters. A NET-related signature was constructed using LASSO regression and verified in four immunotherapy cohorts. ROC and Kaplan-Meier analyses were conducted to evaluate the predictive and prognostic value of the model for immunotherapy efficacy.
This study identified two NET-related clusters with distinct clinicopathological features, prognosis, and TME landscapes. The high NET-related cluster, characterized by increased NET-related gene expression, exhibited more aggressive behavior and a worse prognosis (HR = 1.63, = 0.004) than the low NET-related cluster. DEGs were primarily involved in the chemokine/cytokine-associated pathways. Moreover, the high NET-related cluster had significantly higher levels of TME scores, immune infiltration, and immune effectors (all < 0.001). The NET-related signature displayed a high predictive accuracy for immunotherapy response (AUC = 0.939, < 0.001). Furthermore, patients with high NET-related scores consistently harbored a more favorable prognosis in different immunotherapy cohorts (all < 0.05).
This study identified the NET-related signature as a robust model for predicting immunotherapy response in GC, which can help clinicians make appropriate immunotherapy decisions.
中性粒细胞胞外陷阱（NET）与宿主反应、肿瘤发生及免疫功能障碍相关。然而，NET与胃癌（GC）肿瘤微环境（TME）之间的联系仍不清楚。我们的研究旨在描述NET相关基因在GC队列中的表达模式及其与临床病理特征、预后、TME特征和免疫治疗疗效的关系。
从TCGA-STAD（n = 415）、GSE62254（n = 300）、GSE15459（n = 192）和GSE183904（n = 26）获取具有注释临床病理数据的GC转录组和单细胞RNA测序图谱。使用共识聚类算法将肿瘤样本分类为不同的NET相关簇。使用LASSO回归构建NET相关特征，并在四个免疫治疗队列中进行验证。进行ROC和Kaplan-Meier分析以评估该模型对免疫治疗疗效的预测和预后价值。
本研究确定了两个具有不同临床病理特征、预后和TME格局的NET相关簇。高NET相关簇以NET相关基因表达增加为特征，与低NET相关簇相比，表现出更具侵袭性的行为和更差的预后（HR = 1.63， = 0.004）。差异表达基因主要参与趋化因子/细胞因子相关途径。此外，高NET相关簇的TME评分、免疫浸润和免疫效应因子水平显著更高（均 < 0.001）。NET相关特征对免疫治疗反应显示出较高的预测准确性（AUC = 0.939， < 0.001）。此外，在不同免疫治疗队列中，NET相关评分高的患者始终具有更有利的预后（均 < 0.05）。
本研究确定NET相关特征是预测GC免疫治疗反应的强大模型，可帮助临床医生做出适当的免疫治疗决策。
