Analysis of the differential expression of circulating microRNAs during the progression of hepatic fibrosis in patients with chronic hepatitis B virus infection - PubMed (original) (raw)

Analysis of the differential expression of circulating microRNAs during the progression of hepatic fibrosis in patients with chronic hepatitis B virus infection

Qingqing Zhang et al. Mol Med Rep. 2015 Oct.

Abstract

Considering the limitations of liver biopsy, reliable non‑invasive serum biomarkers of liver fibrosis are required for early diagnosis. The present study analyzed the expression profile of circulating micro (mi)RNAs during the development and progression of hepatic fibrosis in patients with chronic hepatitis B virus (HBV) infection, aiming to identify novel earlier diagnostic biomarkers. Fresh plasma samples were collected from 50 patients diagnosed with chronic HBV infection and hepatic fibrosis. These patients were classified into five groups (S0, S1, S2, S3 and S4; n=10 per group) based on Scheuer's staging criteria. The differential expression of the circulating miRNAs was determined by performing miRNA microarray hybridization. Finally, the target genes of the miRNAs were predicted and classified using gene ontology analysis. A total of 140 miRNAs were detected in the S1‑S4 patient groups, and their expression levels were >2‑fold higher compared with those in the S0 group. The numbers of miRNAs differentially expressed in the S1‑S4 patient groups were 48, 97, 84 and 56, respectively, with 12 miRNAs differentially expressed at all stages, 10 of which were upregulated and two of which were downregulated. The target genes of the miRNAs identified were found to be involved in 100 signal transduction pathways, the majority of which affected hepatic fibrosis via the TGF‑/Smad, Wnt, MAPK, Jak/STAT and VEGF pathways. The differential expression levels of miRNAs were closely associated with the staging of hepatic fibrosis. The results of the present study provide evidence to facilitate the development and application of non‑invasive biomarkers for earlier diagnosis of hepatic fibrosis.

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Figures

Figure 1

Cluster analysis of miRNAs in patients with hepatitis B virus infection and hepatic fibrosis. The horizontal axis on the graph represents the Scheuer stages, the vertical axis indicates plasma miRNAs with altered levels of expression. The intensity of miRNA expression is indicated in green (reduced level of expression) and red (higher level of expression). (A) S1, vs. S0, (B) S2, vs. S0, (C) S3, vs. S0, (D) S4 vs. S0. miRNA, microRNA.

Figure 2

Cluster analysis of differentially expressed miRNAs in different Scheuer's stages. The horizontal axis represents different Scheuer stages (S0–S4), the vertical axis indicates the differentially expressed miRNAs. The intensity of the miRNA expression is indicated in green (lower level of expression) and red (higher level of expression).

Figure 3

Trend analysis of different miRNAs. The expression trends of different miRNAs associated with the progression of hepatic fibrosis is shown. The expression levels of hsa-miR-2861, hsa-miR-345-3p, hsa-miR-3620-3p, hsa-miR-3656, hsa-miR-371a-5p, hsa-miR-4646-5p, hsa-miR-4651, hsa-miR-4695-5p, hsa-miR-4800-5p and hsa-miR-638 were upregulated and the expression levels of hsa-miR-486-3p and hsa-miR-497-5p were downregulated. miR/miRNA, microRNA.

Figure 4

Determination of the GO molecular functions modulated by differentially expressed miRNAs in patients with hepatitis B virus infection and hepatic fibrosis. The target genes were selected based on the GO database. Each GO significance level and misjudgment rate was calculated using Fisher's exact test and a χ2 test (P<0.01). GO, gene ontology.

References

1. Hou J, Liu Z, Gu F. Epidemiology and prevention of hepatitis B virus infection. Int J Med Sci. 2005;2:50. doi: 10.7150/ijms.2.50. - DOI - PMC - PubMed
1. Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism and function. Cell. 2004;116:281–297. doi: 10.1016/S0092-8674(04)00045-5. - DOI - PubMed
1. Vettori S, Gay S, Distler O. Role of MicroRNAs in Fibrosis. Open Rheumatol J. 2012;6:130–139. doi: 10.2174/1874312901206010130. - DOI - PMC - PubMed
1. Ura S, Honda M, Yamashita T, Ueda T, Takatori H, Nishino R, Sunakozaka H, Sakai Y, Horimoto K, Kaneko S. Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology. 2009;49:1098–1112. doi: 10.1002/hep.22749. - DOI - PubMed
1. Wang XW, Heegaard NH, Orum H. MicroRNAs in liver disease. Gastroenterology. 2012;142:1431–1443. doi: 10.1053/j.gastro.2012.04.007. - DOI - PMC - PubMed

Analysis of the differential expression of circulating microRNAs during the progression of hepatic fibrosis in patients with chronic hepatitis B virus infection - PubMed (original) (raw)