Table 4.
Extracellular microRNAs as biomarkers of disease states.a
| Disease | Body fluid | Candidate miRNAs | Cohorts used | Normalizer | Reference | ||
|---|---|---|---|---|---|---|---|
| Discovery | Confirmation | Evaluation | |||||
| Sepsis | Plasma | miR-150 | 8 Sepsis, 8 control leukocytes | 10 Sepsis, 12 control leukocytes | 24 Sepsis, 32 controls | RNU6B, leukocytes; miR-192, plasma | Vasilescu et al. (59) |
| Serum | miR-15a, -16, -223, -499– 5p, -122, -193b* | 166 Sepsis, 32 systemic inflammatory response syndrome (SIRS), 24 controls | 43 Mild, 123 severe sepsis, 24 controls | — | RNU6B | Wang et al. (129) | |
| Serum | miR-146a, -223 | 50 Sepsis, 30 SIRS, 20 controls | — | — | miR-295 | Wang et al. (60) | |
| Systemic lupus erythematosus (SLE) | Serum and urine | miR-200a, -200b, -141, -200c, -429, -205, -192 | 40 SLE, 30 controls– serum | 40 SLE, 30 controls– urine | — | RNU48 | Wang et al. (130) |
| Urine | miR-146a, -155 | 40 SLE, 13 controls | 40 SLE at time 0, 3 and 6 months after treatment | — | RNU48 | Wang et al. (131) | |
| Diabetes mellitus type 2 (DM) | Plasma | miR-126, -15a, -29b, -223, -28–3p | Pooled 2 DM, 6 controls | 99 DM, 99 controls | 822 Different samples | miR-454, RNU6B | Zampetaki et al. (58) |
| Hypertension (Hyp) | Plasma | Human cytomegalovirus miR-UL112, miR-296– 5p, let7e | 13 Hyp, 5 controls | 24 Hyp, 22 controls | 194 Hyp, 67 controls | RNU6B | Li et al. (132) |
| Pulmonary arterial hypertension (PAH) | Plasma | miR-150 | 8 PAH, 8 controls | 145 PAH, 10 controls | 30 PAH | C. elegans miR-39 | Rhodes et al. (133) |
| Multiple sclerosis (MS) | CSF | miR-181c, -633, -922 | Pooled 10 MS, 10 other neurological diseases | 53 MS, 39 other neurological diseases | — | C. elegans miR-39 | Haghikia et al. (61) |
| Plasma | miR-92a-1*, -454, -30e, -22, -210, -574–3p, -135a, -140–3p, let-7a | 9 Secondary progressive MS (SPMS), 10 RRMS, 9 controls | 51 SPMS, 50 relapsing remitting MS (RRMS), 32 controls | 15 Amyotrophic lateral sclerosis | RNA amount | Gandhi et al. (134) | |
| HIV encephalitis (HIVE) | CSF | miR-1224–3p, -204, -484, -720, -934, -937 | 5 HIV+, 4 HIVE, 10 HIV− | — | — | miR-622, -1266 | Pacifici et al. (62) |
| Pregnancy | Serum | miR-520d-5p, -526a, -527 | 20 Pregnant temporal study, 10 controls | — | — | Panel of 6 miRNAs | Gilad et al. (135) |
| Bipolar disorder | Plasma | miR-134 | 21 Bipolar disorder temporal study, 21 controls | — | — | C. elegans lin-4 | Rong et al. (63) |
| Mild cognitive impairment (MCI) | Plasma | Panel of 8 miRNAs | 10 MCI, 10 controls | 20 MCI, 20 Alzheimer disease, 20 controls | 20 young and 20 old controls; 19 retrospective | Ratio of miRNA pairs | Sheinerman et al. (136) |
a
List of 10 different disease conditions in which microRNAs have been evaluated as biomarkers. Each row describes the detection matrix, study design, and normalization method used. Discovery and confirmation steps were typically performed in a cohort with a smaller sample size to select/verify candidate miRNAs, and evaluation was conducted in an expanded cross-sectional or longitudinal cohort to test the specificity, sensitivity, or early diagnostic capability.
Studies were conducted using human biospecimens unless otherwise stated.