BioMed Research International

Review Article

Circulating MicroRNAs for Diagnosis of Acute Pulmonary Embolism: Still a Long Way to Go

Table 1

miRNAs studied as potential diagnostic biomarkers for APE.


Author	Year	Study design	miRNA (cut-off)	Sample	Results	Concerning

Mao et al. [63]	2011	32 APE patients vs. 32 healthy controls vs. 22 non-APE patients	miRNA-134 (10-fold difference between miRNA levels)	Plasma	miRNA-134 was significantly higher in APE with an AUC of 0.83 (95% CI, 0.74 to 0.93)	miRNA-134 was elevated also in UA
Hoekstra et al. [65]	2016	37 APE patients vs. 37 healthy controls	miRNA-28-3p (4-fold difference between miRNA levels)	Plasma	miRNA-28-3p (but neither miRNA-134 nor miRNA-210) show a significant increase—stable during the first 6 hours—in APE. The AUC was 0.79 (95% CI 0.69 to 0.90)	miRNA-28-3p was elevated also in DM and GI malignancies
Zhou et al. [66]	2018	78 APE patients vs. 70 healthy controls	miRNA-27a/b	Plasma	miRNA-27a expression was upregulated in APE patients (). The AUC was 0.78 (95% CI 0.69 to 0.88); . miRNA-27a significantly improved the AUC of D-dimer	miRNA-27 levels are also influenced by LVH
Ba et al. [69]	2016	30 APE patients vs. NSTEMI (), DVT (), PAH (), and 12 healthy controls	miRNA-1233 (11-fold difference between miRNA levels)	Serum	In acute state (1^st day), miRNA-1233 was even able to discriminate APE from NSTEMI with an AUC of 0.95 (95% CI 0.89 to 1.00); highest serum level on 1st day. miRNA-1233 then decreased levels on 3^rd and 5^th day with lower values reached at 9 months	None. Even, miRNA-1233 was better than miRNA-134 and miRNA-27a as APE biomarker
Nie et al. [72]	2018	60 APE vs. 50 healthy controls	miRNA-221 (4-fold difference between miRNA levels)	Plasma	miR-221 was significantly upregulated in APE () and showed positive correlations with BNP, troponin, and D-dimer. AUC for plasma miR-221 was 0.82 (95% CI 0.76 to 0.91), higher than that of D-dimer	miRNA-221 was elevated also in MI and PAH

APE: acute pulmonary embolism; AUC: area under the curve; UA: unstable angina; DM: diabetes mellitus; GI: gastrointestinal; LVH: left ventricular hypertrophy; NSTEMI: non-ST elevated nyocardial infarction; DVT: deep venous thrombosis; PAH: pulmonary arterial hypertension; BNP: B-type natriuretic peptide; MI: myocardial infarction.