越来越多的研究强调了中性粒细胞激活和极化在肿瘤进展中的生物学意义。然而，肿瘤相关中性粒细胞 (TAN) 的特征研究还不够充分。患者的表达谱是从 TCGA、GEO 和 IMvigor210 数据库中获得的。使用六种算法来评估免疫细胞浸润。进行RNA测序以评估诱导的N1样中性粒细胞和N2样中性粒细胞之间的差异表达基因。结合加权基因共表达网络分析 (WGCNA) 和 RNA-seq 数据建立了 TAN 相关风险评分 (TRS) 模型，并在泛癌中进一步评估。招募了 117 名 GC 患者的临床队列，通过免疫组织化学 (IHC) 评估 TAN 在 GC 中的作用。 TRS 特征由 10 个 TAN 相关基因 (TRG) 构建，大多数 TRG 在 GC 微环境的 TAN 中高度丰富。 TRS模型可以准确预测患者的预后以及他们对化疗和免疫治疗的反应。 TRS与促肿瘤免疫细胞呈正相关，与抗肿瘤免疫细胞呈负相关。其他功能分析表明，该特征与泛癌中的促肿瘤和免疫抑制途径（例如缺氧途径）呈正相关。此外，我们的临床队列证明 TAN 是 GC 患者的独立预后因素。本研究构建并证实了一种新型 TRS 模型对于 GC 和泛癌预后预测的价值。对 TRS 和 TAN 的进一步评估将有助于加强对肿瘤微环境的了解并指导更有效的治疗策略。版权所有 © 2024。由 Elsevier Inc. 出版。

An increasing number of studies have highlighted the biological significance of neutrophil activation and polarization in tumor progression. However, the characterization of tumor-associated neutrophils (TANs) is inadequately investigated.Patients' expression profiles were obtained from TCGA, GEO, and IMvigor210 databases. Six algorithms were used to assess immune cell infiltration. RNA sequencing was conducted to evaluate the differentially expressed genes between induced N1- and N2-like neutrophils. A TAN-associated risk score (TRS) model was established using a combination of weighted gene co-expression network analysis (WGCNA) and RNA-seq data and further assessed in pan-cancer. A clinical cohort of 117 GC patients was enrolled to assess the role of TANs in GC via immunohistochemistry (IHC).A TRS signature was built with 10 TAN-related genes (TRGs) and most TRGs were highly abundant in the TANs of the GC microenvironment. The TRS model could accurately predict patients' prognosis, as well as their responses to chemotherapy and immunotherapy. The TRS was positively correlated with pro-tumor immune cells and exhibited negative relationship with anti-tumor immune cells. Additional functional analyses revealed that the signature was positively related to pro-tumor and immunosuppression pathways, such as the hypoxia pathway, across pan-cancer. Furthermore, our clinical cohort demonstrated TANs as an independent prognostic factor for GC patients.This study constructed and confirmed the value of a novel TRS model for prognostic prediction of GC and pan-cancer. Further evaluation of TRS and TANs will help strengthen the understanding of the tumor microenvironment and guide more effective therapeutic strategies.Copyright © 2024. Published by Elsevier Inc.