Guan Bo, Qi Feng, Tian Ye
Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Transl Androl Urol. 2020 Apr;9(2):473-484. doi: 10.21037/tau.2020.01.34.
Wilms tumor (WT) was the most common malignant tumor of urinary system in children. With the advances in gene sequencing, research of molecular mechanism of WT tumor was gradually increasing. However, few studies have explored the influence of competing endogenous RNA (ceRNA) in WT. Accordingly, we aimed to explore the mechanisms of ceRNA co-expression network in WT.
A total of 6 non-tumor controls and 127 WT patients' RNA-seq data combined with clinical data was acquired from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Differentially expressed lncRNA, miRNA and mRNA between WT tissues and normal tissues were analyzed using "edgeR" package in R software. Weighted gene co-expression network analysis (WGCNA) was utilized to construct the ceRNA co-expression network while Molecular Complex Detection (MCODE) algorithm was used to extract the pivotal sub-network. Function annotation of mRNA was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Survival analysis was then conducted based on long-rank test and Kaplan-Meier curves using the survival package.
By applying the "edgeR" package in R, the transcriptome expression data of 127 WT tissues with 6 normal tissues were normalized. Moreover, 146 DElncRNAs, 62 DEmiRNAs, 287 DEmRNAs of them were involved in ceRNA network after applying WGCNA. According to MCODE, we identified that the interactions between LINC002253 (lncRNA) and TRIM71 (mRNA) was mediated by hsa-mir-301a and hsa-mir-301b (miRNA). Furthermore, we detected 13 DElncRNAs which were significantly associated with the progression of WT.
We used WGCNA method to construct the WT ceRNA network for the first time. TRIM71 was identified to be the most closely related genes involved in hub sub-network by MCDOE, suggesting it might act as a new drug target and prognostic factor based on our comprehensive results.
肾母细胞瘤（WT）是儿童泌尿系统最常见的恶性肿瘤。随着基因测序技术的进步，对WT肿瘤分子机制的研究逐渐增多。然而，很少有研究探讨竞争性内源RNA（ceRNA）在WT中的影响。因此，我们旨在探索WT中ceRNA共表达网络的机制。
从治疗应用研究以产生有效治疗方法（TARGET）数据库中获取了总共6个非肿瘤对照和127例WT患者的RNA测序数据以及临床数据。使用R软件中的“edgeR”包分析WT组织与正常组织之间差异表达的lncRNA、miRNA和mRNA。利用加权基因共表达网络分析（WGCNA）构建ceRNA共表达网络，同时使用分子复合物检测（MCODE）算法提取关键子网络。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）对mRNA进行功能注释。然后使用生存包基于长秩检验和Kaplan-Meier曲线进行生存分析。
通过在R中应用“edgeR”包，对127个WT组织和6个正常组织的转录组表达数据进行了标准化。此外，应用WGCNA后，其中146个差异表达lncRNA、62个差异表达miRNA、287个差异表达mRNA参与了ceRNA网络。根据MCODE，我们确定LINC002253（lncRNA）和TRIM71（mRNA）之间的相互作用由hsa-mir-301a和hsa-mir-301b（miRNA）介导。此外，我们检测到13个与WT进展显著相关的差异表达lncRNA。
我们首次使用WGCNA方法构建了WT的ceRNA网络。通过MCDOE确定TRIM71是参与枢纽子网络的最密切相关基因，基于我们的综合结果表明它可能作为新的药物靶点和预后因素。
