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TGIF1 过表达促进胶质瘤进展并恶化患者预后。

TGIF1 overexpression promotes glioma progression and worsens patient prognosis.

机构信息

Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's, Hospital of Henan University, Zhengzhou, People's Republic of China.

Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's, Hospital of Henan University, Zhengzhou, People's Republic of China.

出版信息

Cancer Med. 2022 Dec;11(24):5113-5128. doi: 10.1002/cam4.4822. Epub 2022 May 15.

Abstract

Transforming growth factor β-induced factor homeobox 1 (TGIF1) reportedly promotes the pathological processes of various malignant tumors. However, few studies have investigated the role of TGIF1 in gliomas. We aimed to explore the relationship between TGIF1 expression and the clinical characteristics of patients with glioma, including their overall survival. A total of thousands transcriptome datapoints were downloaded from public databases to determine the correlations between TGIF1 and various clinicopathological features using the Wilcoxon or Kruskal-Wallis tests. The Kaplan-Meier and Cox statistical methods were used to explore the prognostic significance of TGIF1. Gene set enrichment analysis (GSEA) was used to indirectly identify the pathological mechanisms modulated by TGIF1, and compounds that inhibit its expression were determined using a connectivity map (CMap). TGIF1 was significantly overexpressed in gliomas and was correlated with unfavorable prognostic factors and shorter overall survival. Cox analysis confirmed that TGIF1 expression was a significant predictor of poor prognosis in patients with glioma. GSEA revealed that the signaling pathways associated with TGIF1 expression in glioma included extracellular matrix receptor- and cell cycle-modulating proteins. CMap analysis showed that the small molecules scriptaid, torasemide, dexpropranolol, ipratropium bromide, and harmine were potential negative regulators of TGIF1. Finally, in vitro experiments demonstrated that knockdown of TGIF1 significantly inhibited the proliferation and invasion of glioma cell. Taken together, our study, which is the first to comprehensively analyze TGIF1 in gliomas, revealed it to be a novel oncogene in terms of its association with this disease. As such, TGIF1 may be a potential therapeutic target for individualized treatment of patients with glioma.

摘要

转化生长因子β诱导因子同源盒 1(TGIF1)据报道可促进多种恶性肿瘤的病理过程。然而,很少有研究调查 TGIF1 在神经胶质瘤中的作用。我们旨在探讨 TGIF1 表达与神经胶质瘤患者临床特征(包括总生存期)之间的关系。从公共数据库中下载了数千个转录组数据集,使用 Wilcoxon 或 Kruskal-Wallis 检验确定 TGIF1 与各种临床病理特征之间的相关性。Kaplan-Meier 和 Cox 统计方法用于探索 TGIF1 的预后意义。基因集富集分析(GSEA)用于间接确定 TGIF1 调节的病理机制,并使用连接图谱(CMap)确定抑制其表达的化合物。TGIF1 在神经胶质瘤中显著过表达,与不良预后因素和总生存期缩短相关。Cox 分析证实 TGIF1 表达是神经胶质瘤患者预后不良的显著预测因子。GSEA 显示与神经胶质瘤中 TGIF1 表达相关的信号通路包括细胞外基质受体和细胞周期调节蛋白。CMap 分析表明,小分子 scriptaid、torasemide、dexpropranolol、ipratropium bromide 和 harmine 可能是 TGIF1 的潜在负调节剂。最后,体外实验表明,敲低 TGIF1 可显著抑制神经胶质瘤细胞的增殖和侵袭。综上所述,我们的研究首次全面分析了神经胶质瘤中的 TGIF1,表明其作为该疾病的新型癌基因与其相关。因此,TGIF1 可能是神经胶质瘤个体化治疗的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ed/9761070/ec1b07bddcf3/CAM4-11-5113-g001.jpg

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