Serum MicroRNA Levels as a Noninvasive Diagnostic Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Liver Fibrosis
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Background/Aims: To investigate the role of selected serum microRNA (miRNA) levels as potential noninvasive biomarkers for differentiating S0-S2 (early fibrosis) from S3-S4 (late fibrosis) in patients with a chronic hepatitis B virus (HBV) infection. Methods: One hundred twenty-three treatment-naive patients with a chronic HBV infection who underwent a liver biopsy were enrolled in this study. The levels of selected miRNAs were measured using a real-time quantitative polymerase chain reaction assay. A logistic regression analysis was performed to assess factors associated with fibrosis progression. Receiver operating characteristic (ROC) curve and discriminant analyses validated these the ability of these predicted variables to discriminate S0-S2 from S3-S4. Results: Serum miR-29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated as fibrosis progressed from S0-S2 to S3-S4 (p<0.05), but not miR-16. The multivariate logistic regression analysis identified a panel of three miRNAs and platelets that were associated with a high diagnostic accuracy in discriminating S0-S2 from S3-S4, with an area under the curve of 0.936. Conclusions: The levels of the studied miRNAs, with the exception of miR-16, varied with fibrosis progression. A panel was identified that was capable of discriminating S0-S2 from S3-S4, indicating that serum miRNA levels could serve as a potential noninvasive biomarker of fibrosis progression.
Abstract
Background/Aims: To investigate the role of selected serum microRNA (miRNA) levels as potential noninvasive biomarkers for differentiating S0-S2 (early fibrosis) from S3-S4 (late fibrosis) in patients with a chronic hepatitis B virus (HBV) infection. Methods: One hundred twenty-three treatment-naive patients with a chronic HBV infection who underwent a liver biopsy were enrolled in this study. The levels of selected miRNAs were measured using a real-time quantitative polymerase chain reaction assay. A logistic regression analysis was performed to assess factors associated with fibrosis progression. Receiver operating characteristic (ROC) curve and discriminant analyses validated these the ability of these predicted variables to discriminate S0-S2 from S3-S4. Results: Serum miR-29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated as fibrosis progressed from S0-S2 to S3-S4 (p<0.05), but not miR-16. The multivariate logistic regression analysis identified a panel of three miRNAs and platelets that were associated with a high diagnostic accuracy in discriminating S0-S2 from S3-S4, with an area under the curve of 0.936. Conclusions: The levels of the studied miRNAs, with the exception of miR-16, varied with fibrosis progression. A panel was identified that was capable of discriminating S0-S2 from S3-S4, indicating that serum miRNA levels could serve as a potential noninvasive biomarker of fibrosis progression.
참고문헌 (36)
- Song Y, "MicroRNAs contribute to hepatocellular carcinoma", Mini Rev Med Chem, 15, pp.459~466 (2015)
- O’Reilly S, "MicroRNAs in fibrosis: opportunities and challenges", Arthritis Res Ther, 18, pp.11~ (2016)
- Ebrahimi A, "MicroRNAs in lung diseases: recent findings and their pathophysiological implications", Pulm Pharmacol Ther, 34, pp.55~63 (2015)
- Wang F, "Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets", Front Med, 8, pp.404~418 (2014)
- Hayes CN, "MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma", Int J Mol Sci, 17, pp.280~ (2016)
- Huang C, "Serum microRNA-29 levels correlate with disease progression in patients with chronic hepatitis B virus infection", J Dig Dis, 15, pp.614~621 (2014)
- Ogawa T, "Suppression of type I collagen production by microRNA-29b in cultured human stellate cells", Biochem Biophys Res Commun, 391, pp.316~321 (2010)
- Sekiya Y, "Suppression of hepatic stellate cell activation by microRNA-29b", Biochem Biophys Res Commun, 412, pp.74~79 (2011)
- Wang Y, "MiR-29 mediates TGFbeta 1-induced extracellular matrix synthesis through activation of Wnt", beta-catenin pathway in human pulmonary fibroblasts, 2015, pp.23(Suppl 1), S119~S125
- Li J, "MicroRNA-29b inhibits endometrial fibrosis by regulating the Sp1-TGF-beta1", Smad-CTGF axis in a rat model, 2016, pp.23, 386~394
- Gabriely G, "MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators", Mol Cell Biol, 28, pp.5369~5380 (2008)
- Zhao J, "MiR-21 simultaneously regulates ERK1 signaling in HSC activation and hepatocyte EMT in hepatic fibrosis", PLoS One, 9, pp.e108005~ (2014)
- Wei J, "MicroRNA-21 activates hepatic stellate cells via PTEN", Akt signaling, 2013, pp.67, 387~392
- Davis BN, "SMAD proteins control DROSHA-mediated microRNA maturation", Nature, 454, pp.56~61 (2008)
- Zhang J, "miR-21 inhibition reduces liver fibrosis and prevents tumor development by inducing apoptosis of CD24+ progenitor cells", Cancer Res, 75, pp.1859~1867 (2015)
- Naito Y, "MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer", Cancer Sci, 105, pp.228~235 (2014)
- Zhu B, "Increased miR-16 expression induced by hepatitis C virus infection promotes liver fibrosis through downregulation of hepatocyte growth factor and Smad7", Arch Virol, 160, pp.2043~2050 (2015)
- Chim SS, "Detection and characterization of placental microRNAs in maternal plasma", Clin Chem, 54, pp.482~490 (2008)
- Desmet VJ, "Classification of chronic hepatitis: diagnosis, grading and staging", Hepatology, 19, pp.1513~1520 (1994)
- Goldschmidt I, "Circulating miR-21 and miR-29a as markers of disease severity and etiology in cholestatic pediatric liver disease", J Clin Med, 5, pp.pii.E28~ (2016)
- Gupta SK, "miR-21 promotes fibrosis in an acute cardiac allograft transplantation model", Cardiovasc Res, 110, pp.215~226 (2016)
- Liu XJ, "MicroRNA21 promotes interstitial fibrosis via targeting DDAH1: a potential role in renal fibrosis", Mol Cell Biochem, 411, pp.181~189 (2016)
- McClelland AD, "miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7", Clin Sci (Lond), 129, pp.1237~1249 (2015)
- Liu X, "Transforming growth factor-beta-sphingosine kinase 1", S1P signaling upregulates microRNA-21 to promote fibrosis in renal tubular epithelial cells, 2016, pp.241, 265~272
- Hyun J, "MicroRNAs in liver fibrosis: focusing on the interaction with hedgehog signaling", World J Gastroenterol, 22, pp.6652~6662 (2016)
- Povero D, "Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease", PLoS One, 9, pp.e113651~ (2014)
- Shafaei S, "Histological grading and staging of liver and its relation to viral loads in chronic anti-HBe positive hepatitis", Caspian J Intern Med, 4, pp.681~685 (2013)
- Wang K, "Circulating microRNAs, potential biomarkers for drug-induced liver injury", Proc Natl Acad Sci U S A, 106, pp.4402~4407 (2009)
- Cheung O, "Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression", Hepatology, 48, pp.1810~1820 (2008)
- Trebicka J, "Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis", J Hepatol, 58, pp.234~239 (2013)
- Guo CJ, "Changes in microRNAs associated with hepatic stellate cell activation status identify signaling pathways", FEBS J, 276, pp.5163~5176 (2009)
- Van Keuren-Jensen KR, "microRNA changes in liver tissue associated with fibrosis progression in patients with hepatitis C", Liver Int, 36, pp.334~343 (2016)
- El-Ahwany E, "Circulating miRNAs as predictor markers for activation of hepatic stellate cells and progression of HCV-induced liver fibrosis", Electron Physician, 8, pp.1804~1810 (2016)
- Lee CH, "The role of microRNA in pathogenesis and as markers of HCV chronic infection", Curr Drug Targets, 18, pp.756~765 (2017)
- Zhang Q, "Analysis of the differential expression of circulating microRNAs during the progression of hepatic fibrosis in patients with chronic hepatitis B virus infection", Mol Med Rep, 12, pp.5647~5654 (2015)
- Jin BX, "MicroRNA panels as disease biomarkers distinguishing hepatitis B virus infection caused hepatitis and liver cirrhosis", Sci Rep, 5, pp.15026~ (2015)
