Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas
Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas
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DOI：
10.1530/eje-17-0702
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发表时间：
2018-03-01
影响因子：
5.8
通讯作者：
Olarescu, Nicoleta Cristina
中科院分区：
文献类型：
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作者：
Falch, Camilla Maria;Sundaram, Arvind Y. M.;Olarescu, Nicoleta Cristina
目的：缺乏与无功能性促性腺激素腺瘤（GA）侵袭性相关的可靠生物标志物。由于肿瘤残留物的生长是高度可变的，用于生长潜力预测的分子标记物是必要的。我们假设，快速和缓慢生长的GA呈现不同的基因表达谱和可靠的肿瘤生长潜力的生物标志物可以被确定，专注于上皮间质转化（EMT）的具体作用设计和方法：八个GA选择RNA测序平均分为快速和缓慢生长组的肿瘤体积倍增时间（TVDT）中位数（27.75个月）。数据通过tophat 2、cufflinks和cummeRbund pipeline进行分析。基于显著性、倍数变化和途径分析，在20个GA中选择40个基因用于RT-qPCR验证。结果：350个基因表达有显著差异（282个基因在快速组中上调，68个基因下调，P-调节后的差异表达率分别为0.001和0.001），其中282个基因在快速组中上调，68个基因在快速组中下调，P-调节后的差异表达率分别为0.001和0.001
Objective: Reliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast-and slow-growing GAs present different gene expression profiles and reliable biomarkers for tumor growth potential could be identified, focusing on the specific role of epithelial-mesenchymal transition (EMT).Design and methods: Eight GAs selected for RNA sequencing were equally divided into fast-and slow-growing group by the tumor volume doubling time (TVDT) median (27.75 months). Data were analyzed by tophat2, cufflinks and cummeRbund pipeline. 40 genes were selected for RT-qPCR validation in 20 GAs based on significance, fold-change and pathway analyses. The effect of silencing MTDH (metadherin) and EMCN (endomucin) on in vitro migration of human adenoma cells was evaluated.Results: 350 genes were significantly differentially expressed (282 genes upregulated and 68 downregulated in the fast group, P-adjusted