Circulating RNA Molecules as Biomarkers in Liver Disease
Abstract
:1. Introduction
2. Circulating RNA: Sources and Transportation
2.1. Sources of Circulating RNA
2.2. Transport of Extracellular RNA Molecules
2.3. Circulating RNA: “Message in a Bottle”?
3. Circulating RNA as Biomarkers of Liver Injury
3.1. Liver Toxicity
Marker | Condition | Change | Diagnostic Performance | Validation in Independent Cohort | Reference |
---|---|---|---|---|---|
Liver toxicity | |||||
ALB, AMBP | Liver toxicity (DGAL, APAP) * | up | Not reported | N/A | [28] |
ALB, AMBP, APOH, GC | Liver toxicity (various compounds) * | up | Not reported | N/A | [29] |
ALB, FGB, HP | Liver toxicity (DGAL, APAP) * | up | Not reported | N/A | [9] |
miR-122 | Liver toxicity (CBrCl3, CCl4) * | up | Not reported | N/A | [26] |
miR-122, miR-192 | Liver toxicity (APAP) * | up | Not reported | N/A | [30] |
miR-122, miR-192 | Liver toxicity (APAP) | up | Not reported | no | [31] |
Liver pathology (general) | |||||
ALB | HCC, liver cirrhosis, active CHB vs. controls | up | Sensitivity 85.5%, specificity: 92.8% for liver pathology | no | [32] |
miR-885-5p | HCC, CHB and liver cirrhosis vs. control | up | AUC: 0.904, sensitivity 90.53%, specificity: 79.17% for liver pathology | yes | [33] |
miR-1225-5p, -1275, -638, -762, -320c, -451, -1974, -630, -1207-5p, -720, -1246 and -486‑5p | CHC, CHB, NASH, and controls | - | Accuracy of distinction among conditions: 87.5% | yes | [34] |
Chronic hepatitis C | |||||
miR-92a and miR-423 | CHC vs. control | up | AUC: 0.996; sensitivity: 97.9%; specificity: 99.4% | yes | [35] |
miR-1225-5p, -1275, -638, -762, -320c, -451, -1974, -1207-5p and -1246 | CHC vs. control | - | Diagnostic accuracy: 96.6% | yes | [34] |
miR-122, -16, -34a | CHC vs. control | up | Not reported | yes | [36] |
miR-122, miR-16 | Early CHC (F0-F1) vs. control | - | AUC: 0.90 and 0.92, respectively | no | [36] |
miR-483-5p, miR-671-5p | Liver fibrosis in CHC patients | up; correlation | Accuracy 87.5%, OR 14.25 (F0 vs. F1-F3) | no | [34] |
let-7a, miR-106b, -1274a, -130b, -140-3p, -151-3p, -181a, -19b, -21, -24, -375, -548l, -93 and -941 | Liver fibrosis in CHC patients | down; correlation | no | [34] | |
miR-571 | Liver cirrhosis in CHC patients | up | AUC: 0.91 for the presence of cirrhosis | no | [37] |
miR-122 | Liver fibrosis in CHC patients | no correlation | Not reported | no | [38,39] |
miR-122, miR-34a | Liver fibrosis and activity in CHC patients | up; correlation | Not reported | no | [36] |
miR-122 | Necroinflammatory activity in CHC patients | up; correlation | Not reported | no | [38] |
miR-1914 *, -193a-5p, -22, -659 and -711 | Liver inflammation in CHC patients | up; correlation | Accuracy for A1, A2, and A3: 71.9%, 75% and 82.8%, respectively | no | [34] |
miR-1274b, -197, -1974, -21, -34a,-451, -548d-5p, -760 and -767-3p | Liver inflammation in CHC patients | down; correlation | no | [34] | |
Chronic hepatitis B | |||||
miR-375, -92a, -10a, -223, -423, -23b/a, -342-3p, -99a, -122a, -125b, -150 and let-7c | CHB vs. control | up | Not reported | yes | [35] |
miR-375, -10a, -223 and -423 | CHB vs. control | up | AUC: 0.999; sensitivity: 99.3%; specificity: 98.8% | yes | [35] |
miR-122 | CHB vs. control | up | AUC: 0.989 | yes | [40] |
miR-122 | CHB (active) vs. control | up | AUC: 0.762 | no | [41] |
ALB, APOA2, HP, CYP2E1 | CHB (active) vs. control | up | AUC: 0.945, 0.909, 0.834, 0.801, respectively | no | [41] |
miR-122, -638, -575, -572 and -744 | CHB vs. control | - | CHB vs. healthy: AUC: 0.98, 1.00, 0.91, 0.95 and 0.95, respectively | no | [42] |
miR-21, -122 and -223 | CHB vs. control | up | CHB vs. healthy: AUC: 0.91, 0.93, and 0.88, respectively | no | [43] |
miR-99a, -100, -122, -122 *, -125b, -192, -192 *, -193b, -194, -215, -365, -455-5p, -455-3p, -483-3p, -885-5p and -1247 | CHB: HBeAg positive, HBeAg negative and healthy children | up; HBeAg positive > HBeAg negative > healthy | Not reported | no | [44] |
miR-99a-5p, -100-5p, -122-5p, -122-3p, -125b-5p, 192-5p, -192-3p, -193b-3p, -194-5p, -215, -365a-3p, -455-5p, -483-3p and -855-5p | CHB: immunological phases of HBV infection in children | down; immune-tolerant > immune-active > immune-inactive | Not reported | no | [45] |
miR-10a and miR-125b | CHB vs. HBV-positive HCC | up | AUC: 0.992; sensitivity: 98.5%; specificity: 98.5 | yes | [35] |
Hepatocellular carcinoma | |||||
ALB | HCC | up | AUC: 0.72, sensitivity 73%, specificity 70% for prediction of 2-year HCC recurrence | no | [46] |
MiR-21 + AFP (protein) | HCC | up | HCC vs. chronic hepatitis: AUC: 0.773, sensitivity 61.1%, specificity 83.3%. HCC vs. healthy: AUC: 0.953, sensitivity 87.3%, specificity 92.0%. | no | [47] |
miR-122 | HCC vs. control | up | AUC: 0.869, sensitivity 81.6%, specificity 83.3% | yes | [48] |
miR-222, miR-223 | HCC vs. control | up | Not reported | yes | [48] |
miR-21 | HCC vs. control | down | Not reported | yes | [48] |
miR-375 | HCC vs. control | up | AUROC: 0.96, specificity: 96%; sensitivity: 100% | yes | [35] |
miR-375, -25 and let-7f | HCC vs. control | up | AUC: 0.997; sensitivity: 97.9%; specificity: 99.1% | yes | [35] |
miR-23b, -423, -375, -23a and -342-3p | HBV-positive HCC vs. control | up | AUC: 0.999; sensitivity: 96.9%; specificity: 99.4% | yes | [35] |
miR-21, -122 and -223 | HCC vs. control | up | AUC: 0.87, 0.79, and 0.86, respectively. | yes | [43] |
miR-122, -192, -21, -223, -26a, -27a, and -801 | HCC | - | AUC: 0.888; 0.941 (vs. healthy); 0.842 (vs. CHB); 0.884 (vs. cirrhosis) | yes | [49] |
Liver transplantation | |||||
ALB | Liver transplant complications | up | Not reported | no | [50] |
miR-122 and miR-148a | post-transplantation liver injury | up | Not reported | no | [51] |
Non-alcoholic fatty liver disease | |||||
miR-122, miR-16 | Early NAFLD (simple steatosis) vs. control | up | AUC: 0.93 and 0.96, respectively | no | [36] |
miR-122, -638, -575, -572 and -744 | NASH vs. control | - | AUC: 0.80, 0.97, 0.90, 0.85, and 0.96, respectively. | no | [42] |
miR-122, -192, -19a, -19b, -125b and -375 | NAFLD vs. control | up | AUC: ~0.7 (for miR-122, -192 and -375) | yes | [52] |
miR-21, -34a, -122 and -451 | NAFLD vs. control | up | Not reported | no | [53] |
miR-122-5p, -1290, -27b-3p and -192-5p | NAFLD vs. control | up | AUC: 0.856, sensitivity 85.55%, specificity 73.3% | yes | [54] |
3.2. Chronic Viral Hepatitis
3.3. Hepatocellular Carcinoma
3.4. Non-Alcoholic Fatty Liver Disease
3.5. Liver Transplantation
3.6. Prognostic Value of Circulating RNAs in Liver Disease
4. Pre-Analytical and Analytical Challenges in the Assessment of Circulating RNA
5. Conclusions and Perspectives
Conflicts of Interest
References
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Enache, L.S.; Enache, E.L.; Ramière, C.; Diaz, O.; Bancu, L.; Sin, A.; André, P. Circulating RNA Molecules as Biomarkers in Liver Disease. Int. J. Mol. Sci. 2014, 15, 17644-17666. https://doi.org/10.3390/ijms151017644
Enache LS, Enache EL, Ramière C, Diaz O, Bancu L, Sin A, André P. Circulating RNA Molecules as Biomarkers in Liver Disease. International Journal of Molecular Sciences. 2014; 15(10):17644-17666. https://doi.org/10.3390/ijms151017644
Chicago/Turabian StyleEnache, Liviu S., Elena L. Enache, Christophe Ramière, Olivier Diaz, Ligia Bancu, Anca Sin, and Patrice André. 2014. "Circulating RNA Molecules as Biomarkers in Liver Disease" International Journal of Molecular Sciences 15, no. 10: 17644-17666. https://doi.org/10.3390/ijms151017644