PDF(Pubmed)
Abstract：
The laying hen is the spontaneous model of ovarian tumor. A comprehensive comparison based on RNA-seq from hens and women may shed light on the molecular mechanisms of ovarian cancer. We performed next-generation sequencing of microRNA and mRNA expression profiles in 9 chicken ovarian cancers and 4 normal ovaries, which has been deposited in GSE246604. Together with 6 public datasets (GSE21706, GSE40376, GSE18520, GSE27651, GSE66957, TCGA-OV), we conducted a comparative transcriptomics study between chicken and human. In the present study, miR-451, miR-2188-5p, and miR-10b-5p were differentially expressed in normal ovaries, early- and late-stage ovarian cancers. We also disclosed 499 up-regulated genes and 1,061 down-regulated genes in chicken ovarian cancer. The molecular signals from 9 cancer hallmarks, 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and 369 Gene Ontology (GO) pathways exhibited abnormalities in ovarian cancer compared to normal ovaries via Gene Set Enrichment Analysis (GSEA). In the comparative analysis across species, we have uncovered the conservation of 5 KEGG and 76 GO pathways between chicken and human including the mismatch repair and ECM receptor interaction pathways. Moreover, a total of 174 genes contributed to the core enrichment for these KEGG and GO pathways were identified. Among these genes, the 22 genes were found to be associated with overall survival in patients with ovarian cancer. In general, we revealed the microRNA profiles of ovarian cancers in hens and updated the mRNA profiles previously derived from microarrays. And we also disclosed the molecular pathways and core genes of ovarian cancer shared between hens and women, which informs model animal studies and gene-targeted drug development.
摘要：
蛋鸡是卵巢肿瘤的自发性模型。基于来自母鸡和女性的RNA-seq的综合比较可能揭示卵巢癌的分子机制。我们对9个鸡卵巢癌和4个正常卵巢的microRNA和mRNA表达谱进行了下一代测序，已存入GSE246604。连同6个公共数据集(GSE21706,GSE40376,GSE18520,GSE27651,GSE66957,TCGA-OV),我们在鸡和人之间进行了比较转录组学研究。在本研究中,miR-451,miR-2188-5p,miR-10b-5p在正常卵巢中差异表达,早期和晚期卵巢癌。我们还公开了鸡卵巢癌中的499个上调基因和1,061个下调基因。来自9个癌症标志的分子信号，25京都基因和基因组百科全书（KEGG）途径，通过基因集富集分析(GSEA),与正常卵巢相比,369个基因本体论(GO)通路在卵巢癌中表现出异常。在跨物种的比较分析中，我们发现了鸡与人之间5条KEGG和76条GO通路的保守性，包括错配修复和ECM受体相互作用通路。此外，总共174个基因有助于这些KEGG和GO途径的核心富集。在这些基因中,研究发现,这22个基因与卵巢癌患者的总生存期相关.总的来说,我们揭示了母鸡卵巢癌的microRNA谱,并更新了以前来自微阵列的mRNA谱.我们还公开了母鸡和女性之间共有的卵巢癌的分子途径和核心基因，这为模型动物研究和基因靶向药物开发提供了信息。
