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肾上腺皮质癌中下调的枢纽基因的生物信息学筛选与鉴定

Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma.

作者信息

Xu Fangshi, Zhang Peng, Yuan Miao, Yang Xiaojie, Chong Tie

机构信息

Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710000, P.R. China.

Department of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

出版信息

Exp Ther Med. 2020 Sep;20(3):2730-2742. doi: 10.3892/etm.2020.8987. Epub 2020 Jul 10.

Abstract

The molecular mechanisms of adrenocortical carcinoma (ACC) carcinogenesis and progression remain unclear. In the present study, three microarray datasets from the Gene Expression Omnibus database were screened, which identified a total of 96 differentially expressed genes (DEGs). A protein-protein interaction network (PPI) was established for these DEGs and module analysis was performed using STRING and Cytoscape. A total of eight hub genes were identified from the most significant module; namely, calponin 1 (CNN1), myosin light chain kinase (MYLK), cysteine and glycine rich protein 1 (CSRP1), myosin heavy chain 11 (MYH11), fibulin extracellular matrix protein 2 (EFEMP2), fibulin 1 (FBLN1), microfibril associated protein 4 (MFAP4) and fibulin 5 (FBLN5). The biological functions of these hub genes were analyzed using the DAVID online tool. Changes in the expression of hub genes did not affect overall survival; however, downregulated EFEMP2 decreased disease-free survival. CSRP1 and MFAP4 expression levels were associated with adverse clinicopathological features. In conclusion, although all eight hub genes were downregulated in ACC, they appeared to have important functions in ACC carcinogenesis and progression. Identification of these genes complements the genetic expression profile of ACC and provides insight for the diagnosis, treatment and prognosis of ACC.

摘要

肾上腺皮质癌(ACC)发生发展的分子机制仍不清楚。在本研究中,从基因表达综合数据库筛选了三个微阵列数据集,共鉴定出96个差异表达基因(DEG)。为这些DEG建立了蛋白质-蛋白质相互作用网络(PPI),并使用STRING和Cytoscape进行模块分析。从最显著的模块中总共鉴定出8个枢纽基因,即钙调蛋白1(CNN1)、肌球蛋白轻链激酶(MYLK)、富含半胱氨酸和甘氨酸的蛋白1(CSRP1)、肌球蛋白重链11(MYH11)、纤连蛋白细胞外基质蛋白2(EFEMP2)、纤连蛋白1(FBLN1)、微原纤维相关蛋白4(MFAP4)和纤连蛋白5(FBLN5)。使用DAVID在线工具分析这些枢纽基因的生物学功能。枢纽基因表达的变化不影响总生存期;然而,EFEMP2表达下调会降低无病生存期。CSRP1和MFAP4的表达水平与不良临床病理特征相关。总之,虽然所有8个枢纽基因在ACC中均下调,但它们似乎在ACC的发生发展中具有重要功能。这些基因的鉴定补充了ACC的基因表达谱,并为ACC的诊断、治疗和预后提供了思路。

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