与接受重组组织型纤溶酶原激活剂治疗的中风患者发生出血性转化相关的基因。

Genes involved in hemorrhagic transformations that follow recombinant t-PA treatment in stroke patients.

机构信息

Neurovascular Research Laboratory & Neurovascular Unit, Department of Neurology, Vall d'Hebron University Hospital, Departamento de Medicina, Universitat Autonoma de Barcelona, Vall d'Hebron Research Institute, 119-129, 08035 Barcelona, Spain.

出版信息

Pharmacogenomics. 2013 Apr;14(5):495-504. doi: 10.2217/pgs.13.19.

DOI:10.2217/pgs.13.19

PMID:23556447

Abstract

AIM

Despite the benefits of recombinant t-PA (rt-PA) for stroke patients some of them suffer from adverse hemorrhagic transformations (HTs) following treatment. Our objective is to study the transcriptomics of HTs patients.

METHODS

We studied by microarrays 11 blood samples from patients with stroke that had received rt-PA of whom six of them had suffered a HT. For replication step RNA was collected from 14 new subjects (seven with HT, seven without) and then analyzed by real-time PCR. Four proteins were measured by ELISA in 72 new subjects to analyze their role as potential protein biomarkers.

RESULTS

The microarray analysis revealed that 14 genes were altered among the HT patients. The replication study confirmed these results for six genes. Two of them (BCL2 and OLFM4) are associated with apoptosis, whereas the other four (LTF, LCN2 [also known as NGAL], CEACAM8 and CRISP3) are involved in the regulation of neutrophil processes.

CONCLUSION

Our data revealed that genes related to apoptosis and neutrophil regulation pathways could be associated with HTs after rt-PA.

摘要

目的

尽管重组组织型纤溶酶原激活剂（rt-PA）对脑卒中患者有益，但其中一些患者在接受治疗后会出现不良的出血性转化（HTs）。我们的目的是研究 HTs 患者的转录组学。

方法

我们通过微阵列分析了 11 名接受 rt-PA 治疗的脑卒中患者的血液样本，其中 6 名患者发生了 HT。在复制阶段，我们从 14 名新患者（7 名发生 HT，7 名未发生）中收集 RNA，并通过实时 PCR 进行分析。我们在 72 名新患者中测量了 4 种蛋白质，以分析它们作为潜在蛋白生物标志物的作用。