Integrated bioinformatic analysis identifies COL4A3, COL4A4, and KCNJ1 as key biomarkers in Wilms tumor.
Integrated bioinformatic analysis identifies COL4A3, COL4A4, and KCNJ1 as key biomarkers in Wilms tumor.
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发表时间：
2021
影响因子：
1.4
通讯作者：
Changgang Guo;Xiling Jiang;Junsheng Guo;Yanlong Wu;Guochang Bao
中科院分区：
文献类型：
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作者：
Changgang Guo;Xiling Jiang;Junsheng Guo;Yanlong Wu;Guochang Bao
肾母细胞瘤（WT）是最常见的儿科实体瘤之一，在全球范围内影响1/10，000的儿童。WT患者的一个子集具有不良预后，这与晚期和/或复发性疾病的高风险相关。因此，迫切需要候选标记物用于WT的诊断和有效治疗。我们评估了三个mRNA微阵列数据集，以确定正常肾组织和WT组织之间的差异。基因表达谱分析显示130个差异表达基因（DEG）。对DEG进行富集分析和基因本体（GO）以及京都基因和基因组百科全书（KEGG）途径分析。随后，我们建立了一个蛋白质-蛋白质相互作用（PPI）网络，以揭示DEG之间的关联，并选择了10个枢纽基因，所有这些基因在WT中下调。WT组织中COL 4A 3、COL 4A 4、KCNJ 1、MME和SLC 12 A1的表达均显著低于正常肾组织。使用Kaplan-Meier方法进行的生存分析显示，WT和COL 4A 3、COL 4A 4和KCNJ 1低表达的患者总体生存率明显较差。使用cBioPortal分析WT中COL 4A 3、COL 4A 4和KCNJ 1之间的相关性; COL 4A 3、COL 4A 4和KCNJ 1彼此呈正相关。因此，这些基因被认为具有临床意义，因此可能在肿瘤发生和WT的发展中发挥重要作用。
Wilms tumor (WT) is one of the most common pediatric solid tumors, affecting 1 in 10,000 children, worldwide. A subset of WT patients has poor prognosis, which is associated with a high risk of advanced and/or recurrent disease. Therefore, candidate markers are urgently needed for the diagnosis and effective treatment of WT. We evaluated three mRNA microarray datasets to identify the differences between normal kidney tissue and WT tissue. Gene expression profiling revealed 130 differentially expressed genes (DEGs). Enrichment analysis and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for the DEGs. Subsequently, we established a protein-protein interaction (PPI) network to reveal the associations among the DEGs and selected 10 hub genes, all of which were downregulated in WT. The expression of COL4A3, COL4A4, KCNJ1, MME, and SLC12A1 in WT tissues was significantly lower than that in normal renal tissues. Survival analyses using the Kaplan-Meier method showed that patients with WT and low expression of COL4A3, COL4A4, and KCNJ1 exhibited remarkably poor overall survival. The correlations among COL4A3, COL4A4, and KCNJ1 in WT were analyzed using cBioPortal; COL4A3, COL4A4, and KCNJ1 were positively correlated with each other. Thus, these genes were considered clinically significant and might therefore play important roles in carcinogenesis and the development of WT.