Circulating MicroRNAs in Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage

动脉瘤性蛛网膜下腔出血后迟发性脑梗死中的循环微小RNA

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作者:Gang Lu, Man Sze Wong, Mark Zhi Qiang Xiong, Chi Kwan Leung, Xian Wei Su, Jing Ye Zhou, Wai Sang Poon, Vera Zhi Yuan Zheng, Wai Yee Chan, George Kwok Chu Wong

Background

Delayed cerebral infarction (DCI) is a major cause of morbidities after aneurysmal subarachnoid hemorrhage (SAH) and typically starts at day 4 to 7 after initial hemorrhage. MicroRNAs (miRNAs) play an important role in posttranscriptional gene expression control, and distinctive patterns of circulating miRNA changes have been identified for some diseases. We aimed to investigate miRNAs that characterize SAH patients with DCI compared with those without DCI.

Conclusions

We found a 4-miRNA combination that characterized SAH patients with DCI. The findings could guide future mechanistic study to develop therapeutic targets.

Results

Circulating miRNAs were collected on day 7 after SAH in healthy, SAH-free controls (n=20), SAH patients with DCI (n=20), and SAH patients without DCI (n=20). We used the LASSO (least absolute shrinkage and selection operator) method of regression analysis to characterize miRNAs associated with SAH patients with DCI compared with those without DCI. In the 28 dysregulated miRNAs associated with DCI and SAH, we found that a combination of 4 miRNAs (miR-4532, miR-4463, miR-1290, and miR-4793) could differentiate SAH patients with DCI from those without DCI with an area under the curve of 100% (95% CI 1.000-1.000, P<0.001). This 4-miRNA combination could also distinguish SAH patients with or without DCI from healthy controls with areas under the curve of 99.3% (95% CI 0.977-1.000, P<0.001) and 82.0% (95% CI 0.685-0.955, P<0.001), respectively. Conclusions: We found a 4-miRNA combination that characterized SAH patients with DCI. The findings could guide future mechanistic study to develop therapeutic targets.

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