Identification of neutrophil-related genes and development of a prognostic model for cholangiocarcinoma
Identification of neutrophil-related genes and development of a prognostic model for cholangiocarcinoma
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DOI：
10.1002/jgm.3569
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发表时间：
2023-08-02
影响因子：
3.5
通讯作者：
Liu，Longzi
中科院分区：
文献类型：
--
作者：
Li，Jianfeng;Xiong，Jianhui;Liu，Longzi
背景胆管癌是一种常见的胃肠道肿瘤，早期诊断方法有限。中性粒细胞在胆管癌的背景下的作用仍然在很大程度上unexplored.MethodsA的胆管癌样本（TCGA-CHOL）从TCGA数据库队列进行了全面的分析，调查胆管癌和中性粒细胞之间的关系。方法包括单样本基因集富集分析（ssGSEA）、差异表达分析、加权基因共表达网络分析（WGCNA）和基因集富集分析（GSEA）。WGCNA和差异表达分析导致鉴定了由1059个基因组成的中性粒细胞相关基因模块。聚类1显示中性粒细胞比例较高，与较好的生存结局有关。GSEA在第2组中揭示了补体、炎症反应和干扰素反应途径的下调，暗示了可能的胆管癌发展触发因素。在簇1中观察到PD 1、PD-L1和CTLA 4的显著上调，表明免疫治疗的潜在益处。基于临床数据和三个预后基因（SOWAHD、TNFAIP 8和EBF 3）的表达水平开发了预后模型，其显示出令人满意的区分、校准和临床益处。TNFAIP 8在胆管癌细胞中的过表达被发现，其敲低显着抑制细胞增殖和migration.ConclusionsThis研究阐明了中性粒细胞相关的基因模块和预后基因，提供洞察中性粒细胞在胆管癌的发展和进展中的作用。它还介绍了一种临床预测模型，用于增强预后评估。这些发现可能为胆管癌治疗创新策略的发展奠定基础。
BackgroundCholangiocarcinoma is a prevalent gastrointestinal tumor with limited effective early diagnostic methods. The role of neutrophils in the context of cholangiocarcinoma remains largely unexplored.MethodsA comprehensive analysis was performed on a cohort of cholangiocarcinoma samples (TCGA‐CHOL) from the TCGA database to investigate the relationship between cholangiocarcinoma and neutrophils. Methodologies included single‐sample gene set enrichment analysis (ssGSEA), differential expression analysis, weighted gene co‐expression network analysis (WGCNA) and gene set enrichment analysis (GSEA).ResultsThe study identified a significant decrease of neutrophils in cholangiocarcinoma via ssGSEA. WGCNA and differential expression analysis led to the identification of a neutrophil‐related gene module comprised of 1059 genes. Cluster 1, showing a higher proportion of neutrophils, was linked to better survival outcomes. GSEA disclosed downregulation of complement, inflammatory response and interferon response pathways in Cluster 2, hinting at possible cholangiocarcinoma development triggers. A notable upregulation of PD1, PD‐L1 and CTLA4 was observed in Cluster 1, suggesting potential benefits from immunotherapy. A prognostic model was developed based on clinical data and expression levels of three prognostic genes (SOWAHD, TNFAIP8 and EBF3) showing satisfactory discrimination, calibration and clinical benefits. An overexpression of TNFAIP8 in cholangiocarcinoma cells was found, with its knockdown significantly inhibiting cell proliferation and migration.ConclusionsThis study elucidates a neutrophil‐related gene module and prognostic genes, offering insights into the role of neutrophils in cholangiocarcinoma development and progression. It also introduces a clinical prediction model for enhanced prognosis assessment. These findings may lay the groundwork for the development of innovative therapeutic strategies in cholangiocarcinoma treatment.