Gene expression signatures identify paediatric patients with multiple organ dysfunction who require advanced life support in the intensive care unit.
Gene expression signatures identify paediatric patients with multiple organ dysfunction who require advanced life support in the intensive care unit.
复制标题
基因表达特征识别儿科患者多器官功能障碍谁需要在重症监护病房的高级生命支持。
DOI：
10.1016/j.ebiom.2020.103122
复制
发表时间：
2020-12
期刊：
影响因子：
11.1
通讯作者：
Rajasekaran S
中科院分区：
文献类型：
--
作者：
Shankar R;Leimanis ML;Newbury PA;Liu K;Xing J;Nedveck D;Kort EJ;Prokop JW;Zhou G;Bachmann AS;Chen B;Rajasekaran S
Multiple organ dysfunction syndrome (MODS) occurs in the setting of a variety of pathologies including infection and trauma. Some patients decompensate and require Veno-Arterial extra corporeal membrane oxygenation (ECMO) as a palliating manoeuvre for recovery of cardiopulmonary function. The molecular mechanisms driving progression from MODS to cardiopulmonary collapse remain incompletely understood, and no biomarkers have been defined to identify those MODS patients at highest risk for progression to requiring ECMO support. Whole blood RNA-seq profiling was performed for 23 MODS patients at three time points during their ICU stay (at diagnosis of MODS, 72 hours after, and 8 days later), as well as four healthy controls undergoing routine sedation. Of the 23 MODS patients, six required ECMO support (ECMO patients). The predictive power of conventional demographic and clinical features was quantified for differentiating the MODS and ECMO patients. We then compared the performance of markers derived from transcriptomic profiling including transcriptomically imputed leukocyte subtype distribution, relevant published gene signatures and a novel differential gene expression signature computed from our data set. The predictive power of our novel gene expression signature was then validated using independently published datasets. None of the five demographic characteristics and 14 clinical features, including The Paediatric Logistic Organ Dysfunction (PELOD) score, could predict deterioration of MODS to ECMO at baseline. From previously published sepsis signatures, only the signatures positively associated with patient's mortality could differentiate ECMO patients from MODS patients, when applied to our transcriptomic dataset (P-value ranges from 0.01 to 0.04, Student's test). Deconvolution of bulk RNA-Seq samples suggested that lower neutrophil counts were associated with increased risk of progression from MODS to ECMO (P-value = 0.03, logistic regression, OR=2.82 [95% CI 0.63 - 12.45]). A total of 30 genes were differentially expressed between ECMO and MODS patients at baseline (log2 fold change ≥ 1 or ≤ -1 with false discovery rate ≤ 0.01). These genes are involved in protein maintenance and epigenetic-related processes. Further univariate analysis of these 30 genes suggested a signature of seven DE genes associated with ECMO (OR > 3.0, P-value ≤ 0.05, logistic regression). Notably, this contains a set of histone marker genes, including H1F0, HIST2H3C, HIST1H2AI, HIST1H4, HIST1H2BL and HIST1H1B, that were highly expressed in ECMO. A risk score derived from expression of these genes differentiated ECMO and MODS patients in our dataset (AUC = 0.91, 95% CI 0.79-1.00, P-value = 7e-04, logistic regression) as well as validation dataset (AUC= 0.73, 95% CI 0.53-0.93, P-value = 2e-02, logistic regression). This study demonstrates that transcriptomic features can serve as indicators of severity that could be superior to traditional methods of ascertaining acuity in MODS patients. Analysis of expression of signatures identified in this study could help clinicians in the diagnosis and prognostication of MODS patients after arrival to the Hospital.
登录
查看更多内容
DOI：
10.1007/978-1-4939-3005-0_1
发表时间：
2016-01-01
期刊：
EXTRACORPOREAL LIFE SUPPORT FOR ADULTS
影响因子：
--
作者：
Brain, Matthew J.;Butt, Warwick W.;MacLaren, Graeme
通讯作者：
MacLaren, Graeme
影响因子：
15.1
作者：
Bestati, Nawar;Leteurtre, Stephane;Leclerc, Francis
通讯作者：
Leclerc, Francis
影响因子：
1.9
作者：
Donkena KV;Young CY;Tindall DJ
通讯作者：
Tindall DJ
双调蛋白可能是经典活化巨噬细胞的新生物标志物
DOI：
10.1016/j.bbrc.2015.09.037
发表时间：
2015-10-23
影响因子：
3.1
作者：
Meng, Chen;Liu, Guilin;Xu, Younian
通讯作者：
Xu, Younian
DOI：
10.1186/s13054-014-0543-8
发表时间：
2014-09-24
期刊：
Critical care (London, England)
影响因子：
--
作者：
Ekaney ML;Otto GP;Sossdorf M;Sponholz C;Boehringer M;Loesche W;Rittirsch D;Wilharm A;Kurzai O;Bauer M;Claus RA
通讯作者：
Claus RA