Hirschsprung's disease (HSCR) is a common newborn defect. This study aimed to identify critical genes involved in the development of HSCR. Differently expressed genes (DEGs) of public data set GSE98502 were analyzed using paired t-test. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.8. Besides, Coexpression network of long noncoding RNAs (lncRNAs)-mRNAs (message RNA) were constructed using weighted gene coexpression network analysis. The key modules were filtered out by calculating the module-trait correlations. Then, hub genes were screened and the expression of these genes was further validated in an independent data set GSE96854. We identified 864 DEGs enriched in 19 GO biological functions such as negative regulation of growth and regulation of heart contraction; 11 KEGG pathways such as mineral absorption and protein digestion and absorption. lncRNAs-mRNAs coexpressed network was constructed, including 8 modules and 177 genes. Hub lncRNAs, including LINC00619, LINC00924, LINC00261, and DRAIC, were identified. Hub mRNAs, including CYCS, CCND1, BDKRB, ITGA6, and TNNC1, were mainly enriched in cancer pathways, p53 signaling pathway, and calcium signaling pathway. The expressions of the hub mRNAs were successfully validated by another independent GSE96854 data set. Our findings indicated the hub lncRNAs, including LINC00619, LINC00924, LINC00261, and DRAIC, as well as hub mRNAs, including CYCS, CCND1, BDKRB, ITGA6, and TNNC1, might involve in the progression of HSCR, and these genes might provide new clinical biomarkers for risk evaluation of HSCR.

中文翻译：

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加权基因共表达网络分析揭示了先天性巨结肠疾病发展中的关键 lncRNA 和 mRNA。

先天性巨结肠 (HSCR) 是一种常见的新生儿缺陷。本研究旨在鉴定参与 HSCR 发展的关键基因。使用配对t-分析公共数据集 GSE98502 的差异表达基因 (DEG)测试。使用注释、可视化和集成发现数据库 (DAVID) 6.8 进行基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 通路富集分析。此外，使用加权基因共表达网络分析构建了长链非编码RNA（lncRNA）-mRNA（信息RNA）的共表达网络。通过计算模块特征相关性过滤掉关键模块。然后，筛选枢纽基因，并在独立数据集 GSE96854 中进一步验证这些基因的表达。我们鉴定了 864 个富含 19 种 GO 生物学功能的 DEG，例如生长负调节和心脏收缩调节；矿物质吸收、蛋白质消化吸收等11条KEGG通路。构建了lncRNAs-mRNAs共表达网络，包括8个模块和177个基因。鉴定了 LINC00619、LINC00924、LINC00261和DRAIC。Hub mRNAs，包括CYCS、CCND1、BDKRB、ITGA6和TNNC1，主要富集在癌症通路、p53信号通路和钙信号通路中。另一个独立的 GSE96854 数据集成功验证了 hub mRNA 的表达。我们的研究结果表明中枢 lncRNA，包括LINC00619、LINC00924、LINC00261和DRAIC，以及中枢 mRNA，包括CYCS、CCND1、BDKRB、ITGA6和TNNC1可能参与HSCR的进展，这些基因可能为HSCR的风险评估提供新的临床生物标志物。