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上调并作为透明细胞肾细胞癌的潜在预后基因。

Upregulated and act as potential prognostic genes for clear cell renal cell carcinoma.

作者信息

Wang Xilong, Zhang Jun, Wang Yangyun, Tu Minqi, Wang Ying, Shi Guowei

机构信息

Department of Urology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.

出版信息

Onco Targets Ther. 2018 Mar 26;11:1697-1706. doi: 10.2147/OTT.S150565. eCollection 2018.

Abstract

PURPOSE

As a typical hypervascular tumor, clear cell renal cell carcinoma (ccRCC) is the most common type of RCC. This study was aimed to explore the prognostic genes for ccRCC, focusing on the roles of vascular endothelial growth factor A () and Delta-like ligand 4 () in the disease.

MATERIALS AND METHODS

The mRNA-sequencing data of kidney renal clear cell carcinoma (KIRC) were obtained from The Cancer Genome Atlas (TCGA) database, including 469 tumor samples and 68 adjacent normal samples. Using limma package, differentially expressed genes (DEGs) were analyzed by differential expression and subgroup analyses and confirmed using validation dataset GSE53757. Followed by enrichment analysis, protein-protein interaction (PPI) network analysis and protein subcellular localization were performed using multifaceted analysis tool for human transcriptome tool, and Cytoscape software and InnateDB database, respectively. Moreover, survival analysis was conducted to identify key prognosis-associated genes. In addition, and levels were detected using real-time quantitative PCR (qRT-PCR).

RESULTS

A total of 1,984 DEGs were screened in the KIRC tumor samples. was located in extracellular space and could interact with placental growth factor (PGF) and angiopoietin 2 (ANGPT2) in the PPI network. Subgroup analysis suggested that was significantly upregulated in stages I, II, and III ccRCC tumor samples. Survival analysis showed that was among the top four prognosis-associated genes. qRT-PCR analysis confirmed that the expression levels of and were significantly upregulated in tumor samples.

CONCLUSION

and might be prognostic genes for ccRCC. Besides, , , and might also be related to the prognosis of ccRCC patients.

摘要

目的

透明细胞肾细胞癌(ccRCC)作为一种典型的富血管肿瘤,是肾细胞癌最常见的类型。本研究旨在探索ccRCC的预后相关基因,重点关注血管内皮生长因子A(VEGF-A)和Delta样配体4(DLL4)在该疾病中的作用。

材料与方法

从癌症基因组图谱(TCGA)数据库获取肾透明细胞癌(KIRC)的mRNA测序数据,包括469个肿瘤样本和68个相邻正常样本。使用limma软件包,通过差异表达和亚组分析对差异表达基因(DEG)进行分析,并使用验证数据集GSE53757进行确认。随后进行富集分析,分别使用人类转录组多面分析工具、Cytoscape软件和InnateDB数据库进行蛋白质-蛋白质相互作用(PPI)网络分析和蛋白质亚细胞定位。此外,进行生存分析以鉴定关键的预后相关基因。另外,使用实时定量PCR(qRT-PCR)检测VEGF-A和DLL4水平。

结果

在KIRC肿瘤样本中总共筛选出1984个DEG。VEGF-A位于细胞外空间,并且在PPI网络中可与胎盘生长因子(PGF)和血管生成素2(ANGPT2)相互作用。亚组分析表明,VEGF-A在I、II和III期ccRCC肿瘤样本中显著上调。生存分析显示,VEGF-A是预后相关的前四个基因之一。qRT-PCR分析证实,肿瘤样本中VEGF-A和DLL4的表达水平显著上调。

结论

VEGF-A和DLL4可能是ccRCC的预后基因。此外,PGF、ANGPT2和DLL4也可能与ccRCC患者的预后相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/5875410/cea00dab98bd/ott-11-1697Fig1.jpg

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