Cell-Free Nucleic Acids for Early Diagnosis of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Rapid identification of acute ischemic stroke (AIS) is challenging in both pre-hospital and hospital settings. We aimed to identify the most promising cell-free nucleic acids (cfNAs) as diagnostic biomarkers for IS within 72 h from symptom onset. We searched PubMed, Web of Science, EMBASE, and Cochrane Library for published articles that evaluated blood cfNAs in the early diagnosis of AIS until 10 May 2023. The diagnostic performances of individual cfNAs were pooled by random-effects meta-analysis based on the fold change of biomarkers' level between AIS and non-AIS patients. Of 2955 records, 66 articles reporting 143 different cfNAs met the inclusion criteria. The median sample size was 110, and 21.4% of the studies performed validation. Among selected high-quality studies, miR-106b-5p, miR-124, miR-155, lncRNA H19, and cfDNA showed good diagnostic performance. Data from four studies on cfDNA involving 355 AIS patients and 97 controls were pooled in the meta-analysis, which showed a significant fold change between AIS and controls (pooled ratio 1.48, 95% confidence interval 1.23-1.79, < 0.001). This review highlights that cfDNA, miR-106b-5p, miR-124, miR-155, and lncRNA H19 are the most promising biomarkers for AIS diagnosis, and further research is needed for verification.