Yang Hailing, Huo Pengfei, Hu Guozhang, Wei Bo, Kong Dalian, Li Hongjun
Emergency Department, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Intensive Care Unit, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Oncol Lett. 2017 Jun;13(6):4755-4761. doi: 10.3892/ol.2017.6084. Epub 2017 Apr 24.
The present study aimed to screen potential target genes for the early diagnosis and treatment of early metastatic clear cell renal cell carcinoma (ccRCC) using the microarray data of early metastatic and non-metastatic ccRCC samples. The DNA microarray dataset GSE47352 was downloaded from Gene Expression Omnibus and included 4 early metastatic and 5 non-metastatic ccRCC samples. Differentially expressed genes (DEGs) were screened using the limma package. Then, pheatmap package was used to conduct two-way clustering for the DEGs. Subsequently, MAPPFinder and GenMAPP were employed separately to perform functional and pathway enrichment analysis for the DEGs. Additionally, a protein-protein interaction (PPI) network was constructed using Cytoscape, and small drug molecules were searched using Connectivity map (cmap). In total, 196 upregulated and 163 downregulated genes were identified. DEGs, including JUN, tumor necrosis factor (TNF), Ras homolog family member B (RHOB) and transforming growth factor β2 (TGFβ2) were significantly enriched in the signaling pathway of renal cell carcinoma. Furthermore, nuclear receptor subfamily 4 group A member 1 (NR4A1) was significantly enriched in the mitogen-activated protein kinase signaling pathway; in addition, laminin subunit α (LAMA) 1, LAMA2 and LAMA4 were significantly enriched in extracellular matrix-receptor interaction. JUN (degree=6) had the highest degree in the PPI network. Thapsigargin (score=-0.913) possessed the highest performance in terms of the treatment of early metastatic ccRCC. In the present study, it was discovered that certain DEGs, including JUN, TNF, RHOB, NR4A1, TGFβ2, LAMA1, LAMA2 and LAMA4 were potential target genes associated with early metastatic ccRCC. In addition, thapsigargin could be used as an efficient small drug molecule for the treatment of early metastatic ccRCC.
本研究旨在利用早期转移性和非转移性透明细胞肾细胞癌（ccRCC）样本的微阵列数据，筛选早期转移性ccRCC早期诊断和治疗的潜在靶基因。DNA微阵列数据集GSE47352从基因表达综合数据库下载，包括4个早期转移性和5个非转移性ccRCC样本。使用limma软件包筛选差异表达基因（DEGs）。然后，使用pheatmap软件包对DEGs进行双向聚类。随后，分别使用MAPPFinder和GenMAPP对DEGs进行功能和通路富集分析。此外，使用Cytoscape构建蛋白质-蛋白质相互作用（PPI）网络，并使用连通性图谱（cmap）搜索小分子药物。总共鉴定出196个上调基因和163个下调基因。包括JUN、肿瘤坏死因子（TNF）、Ras同源家族成员B（RHOB）和转化生长因子β2（TGFβ2）在内的DEGs在肾细胞癌信号通路中显著富集。此外，核受体亚家族4 A组成员1（NR4A1）在丝裂原活化蛋白激酶信号通路中显著富集；此外，层粘连蛋白亚基α（LAMA）1、LAMA2和LAMA4在细胞外基质-受体相互作用中显著富集。JUN（度=6）在PPI网络中度数最高。毒胡萝卜素（得分=-0.913）在早期转移性ccRCC治疗方面表现最佳。在本研究中，发现某些DEGs，包括JUN、TNF、RHOB、NR4A1、TGFβ2、LAMA1、LAMA2和LAMA4是与早期转移性ccRCC相关联的潜在靶基因。此外，毒胡萝卜素可作为治疗早期转移性ccRCC的有效小分子药物。
