Gene expression signatures predict response to therapy with growth hormone.
Gene expression signatures predict response to therapy with growth hormone.
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DOI：
10.1038/s41397-021-00237-5
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Clayton P
中科院分区：
文献类型：
--
作者：
Stevens A;Murray P;De Leonibus C;Garner T;Koledova E;Ambler G;Kapelari K;Binder G;Maghnie M;Zucchini S;Bashnina E;Skorodok J;Yeste D;Belgorosky A;Siguero JL;Coutant R;Vangsøy-Hansen E;Hagenäs L;Dahlgren J;Deal C;Chatelain P;Clayton P
重组人生长激素(r-hGH)被用于治疗生长激素缺乏症(GHD)和Turner综合征(TS)等生长障碍。治疗费用高昂，目前模拟反应的方法也不准确。纳入生长激素缺乏症(n = )71例和TS患者(n = 43)，研究r-hGH治疗5年后的疗效。使用1219个遗传标记和基线(治疗前)血液转录组进行分析。随机森林被用来确定与生长反应相关的转录数据的预测价值。没有遗传标记通过预测的严格标准。然而，我们在生长激素缺乏症和TS中发现了一组相同的基因，它们的表达可以用来高精度地分类r-hGH的治疗反应(AuC >； 0.9)。结合转录标记物和临床表型，可以显著减少预测误差。这项工作可以转化为与预测算法相联系的单一基因组测试，以改善临床管理。试验注册号：NCT00256126和NCT00699855。
Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.
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影响因子：
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作者：
Gerber T;Willscher E;Loeffler-Wirth H;Hopp L;Schadendorf D;Schartl M;Anderegg U;Camp G;Treutlein B;Binder H;Kunz M
通讯作者：
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