Sitras V, Fenton C, Acharya G
Department of Obstetrics and Fetal Medicine, Oslo University Hospital, Rikshospitalet, Norway.
Microarray Resource Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway.
Placenta. 2015 Feb;36(2):170-8. doi: 10.1016/j.placenta.2014.11.017. Epub 2014 Dec 11.
Cardiovascular disease (CVD) and preeclampsia (PE) share common clinical features. We aimed to identify common transcriptomic signatures involved in CVD and PE in humans.
Meta-analysis of individual raw microarray data deposited in GEO, obtained from blood samples of patients with CVD versus controls and placental samples from women with PE versus healthy women with uncomplicated pregnancies. Annotation of cases versus control samples was taken directly from the microarray documentation. Genes that showed a significant differential expression in the majority of experiments were selected for subsequent analysis. Hypergeometric gene list analysis was performed using Bioconductor GOstats package. Bioinformatic analysis was performed in PANTHER.
Seven studies in CVD and 5 studies in PE were eligible for meta-analysis. A total of 181 genes were found to be differentially expressed in microarray studies investigating gene expression in blood samples obtained from patients with CVD compared to controls and 925 genes were differentially expressed between preeclamptic and healthy placentas. Among these differentially expressed genes, 22 were common between CVD and PE.
Bioinformatic analysis of these genes revealed oxidative stress, p-53 pathway feedback, inflammation mediated by chemokines and cytokines, interleukin signaling, B-cell activation, PDGF signaling, Wnt signaling, integrin signaling and Alzheimer disease pathways to be involved in the pathophysiology of both CVD and PE. Metabolism, development, response to stimulus, immune response and cell communication were the associated biologic processes in both conditions. Gene set enrichment analysis showed the following overlapping pathways between CVD and PE: TGF-β-signaling, apoptosis, graft-versus-host disease, allograft rejection, chemokine signaling, steroid hormone synthesis, type I and II diabetes mellitus, VEGF signaling, pathways in cancer, GNRH signaling, Huntingtons disease and Notch signaling.
CVD and PE share same common traits in their gene expression profile indicating common pathways in their pathophysiology.
心血管疾病(CVD)和先兆子痫(PE)具有共同的临床特征。我们旨在确定人类CVD和PE中涉及的共同转录组特征。
对存于基因表达综合数据库(GEO)中的个体原始微阵列数据进行荟萃分析,数据来自CVD患者与对照的血样以及PE女性与正常妊娠健康女性的胎盘样本。病例与对照样本的注释直接取自微阵列文档。选择在大多数实验中显示出显著差异表达的基因进行后续分析。使用Bioconductor GOstats软件包进行超几何基因列表分析。在PANTHER中进行生物信息学分析。
7项CVD研究和5项PE研究符合荟萃分析条件。在调查CVD患者与对照血样中基因表达的微阵列研究中,共发现181个基因差异表达,而在先兆子痫胎盘与健康胎盘之间有925个基因差异表达。在这些差异表达基因中,CVD和PE之间有22个是共同的。
对这些基因的生物信息学分析显示,氧化应激、p-53途径反馈、趋化因子和细胞因子介导的炎症、白细胞介素信号传导、B细胞活化、血小板衍生生长因子(PDGF)信号传导、Wnt信号传导、整合素信号传导和阿尔茨海默病途径参与了CVD和PE的病理生理过程。代谢、发育、对刺激的反应、免疫反应和细胞通讯是两种情况下相关的生物学过程。基因集富集分析显示CVD和PE之间有以下重叠途径:转化生长因子-β(TGF-β)信号传导、凋亡、移植物抗宿主病、同种异体移植排斥、趋化因子信号传导、类固醇激素合成、I型和II型糖尿病、血管内皮生长因子(VEGF)信号传导、癌症途径、促性腺激素释放激素(GNRH)信号传导、亨廷顿病和Notch信号传导。
CVD和PE在基因表达谱上具有相同的共同特征,表明它们在病理生理过程中有共同途径。