RNA 测序发现与胶质母细胞瘤患者静脉血栓栓塞相关的基因和信号通路：病例对照研究。
RNA-sequencing to discover genes and signaling pathways associated with venous thromboembolism in glioblastoma patients: A case-control study.
发表日期：2023 Oct 29
作者：
Maaike Y Kapteijn, Vincent R Lanting, Fleur H J Kaptein, Noori A M Guman, El Houari Laghmani, Thomas B Kuipers, Hailiang Mei, Jelle J Goeman, Frits I Mulder, Sjoerd G van Duinen, Martin J B Taphoorn, Linda Dirven, Marike L D Broekman, Nick van Es, Frederikus A Klok, Johan A F Koekkoek, Henri H Versteeg, Jeroen T Buijs
来源：
THROMBOSIS RESEARCH
摘要：
胶质母细胞瘤患者发生静脉血栓栓塞（VTE）的风险很高。肿瘤内在特征被认为发挥了一定作用，但其潜在的病理生理机制仍不完全清楚。通过使用下一代 RNA 测序 (RNA-Seq) 来识别与胶质母细胞瘤相关 VTE 相关的肿瘤表达基因和信号通路。使用非配对分析比较了 23 名患有 VTE 的胶质母细胞瘤患者和 23 名不患有 VTE 的胶质母细胞瘤患者的肿瘤基因表达谱。对前 50 个差异表达基因进行 Ingenuity Pathway Analysis (IPA) 核心分析，探索相关功能和通路。基于完整的 RNA-Seq 数据，通过聚类分析确定分子胶质母细胞瘤亚型。在 19,327 个基因中，有 1246 个基因 (6.4%) 在患有和不患有 VTE 的胶质母细胞瘤患者之间存在差异表达（未经调整 P < 0.05）。过度表达程度最高的基因是 GLI1，它是 Sonic Hedgehog (Shh) 信号通路中的经典靶基因（log2 倍数变化：3.7；未调整 P < 0.0001，调整 P = 0.219）。同样，Shh 信号传导是与 VTE 相关的最重要的经典途径和过程之一。 VTE 患者中原神经/神经胶质母细胞瘤亚型患者的比例高于对照组。Shh 信号传导可能参与胶质母细胞瘤相关 VTE 的发生。版权所有 © 2023 作者。由爱思唯尔有限公司出版。保留所有权利。
Glioblastoma patients are at high risk of developing venous thromboembolism (VTE). Tumor-intrinsic features are considered to play a role, but the underlying pathophysiological mechanisms remain incompletely understood.To identify tumor-expressed genes and signaling pathways that associate with glioblastoma-related VTE by using next generation RNA-sequencing (RNA-Seq).The tumor gene expression profile of 23 glioblastoma patients with VTE and 23 glioblastoma patients without VTE was compared using an unpaired analysis. Ingenuity Pathway Analysis (IPA) core analysis was performed on the top 50 differentially expressed genes to explore associated functions and pathways. Based on full RNA-Seq data, molecular glioblastoma subtypes were determined by performing cluster analysis.Of the 19,327 genes, 1246 (6.4 %) were differentially expressed between glioblastoma patients with and without VTE (unadjusted P < 0.05). The most highly overexpressed gene was GLI1, a classical target gene in the Sonic Hedgehog (Shh) signaling pathway (log2 fold change: 3.7; unadjusted P < 0.0001, adjusted P = 0.219). In line, Shh signaling was among the top canonical pathways and processes associated with VTE. The proportion of patients with the proneural/neural glioblastoma subtype was higher among those with VTE than controls.Shh signaling may be involved in the development of glioblastoma-related VTE.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.