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用于鉴定影响透明细胞肾细胞癌发病机制的潜在关键基因的综合生物信息学分析

Integrated bioinformatics analysis for the identification of potential key genes affecting the pathogenesis of clear cell renal cell carcinoma.

作者信息

Cui Hao, Xu Lei, Li Zhi, Hou Ke-Zuo, Che Xiao-Fang, Liu Bo-Fang, Liu Yun-Peng, Qu Xiu-Juan

机构信息

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

出版信息

Oncol Lett. 2020 Aug;20(2):1573-1584. doi: 10.3892/ol.2020.11703. Epub 2020 Jun 5.

DOI:10.3892/ol.2020.11703
PMID:32724399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7377202/
Abstract

Clear cell renal cell carcinoma (CCRCC) is a typical type of RCC with the worst prognosis among the common epithelial neoplasms of the kidney. However, its molecular pathogenesis remains unknown. Therefore, the aim of the present study was to screen for effective and potential pathogenic biomarkers of CCRCC. The gene expression profile of the GSE16441, GSE36895, GSE40435, GSE46699, GSE66270 and GSE71963 datasets were downloaded from the Gene Expression Omnibus database. First, the limma package in R language was used to identify differentially expressed genes (DEGs) in each dataset. The robust and strong DEGs were explored using the robust rank aggregation method. A total of 980 markedly robust DEGs were identified (429 upregulated and 551 downregulated). According to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, these DEGs exhibited an obvious enrichment in various cancer-related biological pathways and functions. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used for the construction of a protein-protein interaction (PPI) network, the Cytoscape MCODE plug-in for module analysis and the cytoHubba plug-in to identify hub genes from the aforementioned DEGs. A total of four key modules were identified in the PPI network. A total of six hub genes, including C-X-C motif chemokine ligand 12, bradykinin receptor B2, adenylate cyclase 7, calcium sensing receptor (CASR), kininogen 1 and lysophosphatidic acid receptor 5, were identified. The DEG results of the hub genes were verified using The Cancer Genome Atlas database, and CASR was found to be significantly associated with the prognosis of patients with CCRCC. In conclusion, the present study provided new insight and potential biomarkers for the diagnosis and prognosis of CCRCC.

摘要

透明细胞肾细胞癌(CCRCC)是肾细胞癌的一种典型类型,在常见的肾上皮性肿瘤中预后最差。然而,其分子发病机制仍不清楚。因此,本研究的目的是筛选CCRCC有效的潜在致病生物标志物。从基因表达综合数据库下载了GSE16441、GSE36895、GSE40435、GSE46699、GSE66270和GSE71963数据集的基因表达谱。首先,使用R语言中的limma软件包识别每个数据集中的差异表达基因(DEG)。使用稳健秩聚合方法探索稳健且显著的DEG。共鉴定出980个明显稳健的DEG(429个上调和551个下调)。根据基因本体论和京都基因与基因组百科全书通路富集分析,这些DEG在各种癌症相关的生物学通路和功能中表现出明显的富集。使用检索相互作用基因/蛋白质数据库的搜索工具构建蛋白质-蛋白质相互作用(PPI)网络,使用Cytoscape MCODE插件进行模块分析,并使用cytoHubba插件从上述DEG中识别枢纽基因。在PPI网络中总共鉴定出四个关键模块。共鉴定出六个枢纽基因,包括C-X-C基序趋化因子配体12、缓激肽受体B2、腺苷酸环化酶7、钙敏感受体(CASR)、激肽原1和溶血磷脂酸受体5。使用癌症基因组图谱数据库验证了枢纽基因的DEG结果,发现CASR与CCRCC患者的预后显著相关。总之,本研究为CCRCC的诊断和预后提供了新的见解和潜在的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/10b39a73ecdd/ol-20-02-1573-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/6ca2d3354066/ol-20-02-1573-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/44de5675dac0/ol-20-02-1573-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/db0318458265/ol-20-02-1573-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/5baa818ff38c/ol-20-02-1573-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/69a4a30aef1c/ol-20-02-1573-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/10b39a73ecdd/ol-20-02-1573-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/6ca2d3354066/ol-20-02-1573-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/44de5675dac0/ol-20-02-1573-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/db0318458265/ol-20-02-1573-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/5baa818ff38c/ol-20-02-1573-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/69a4a30aef1c/ol-20-02-1573-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9540/7377202/10b39a73ecdd/ol-20-02-1573-g05.jpg

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