The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B

Abstract

Background and Aim. miRNAs play an important role in the development of human fibrosis. However, miRNA expression profiles during different stages of chronic hepatitis B (CHB) are not well defined. In this study, we aimed to further validate the features of 5 miRNA candidates from our previous study during different fibrotic stages and the value of diagnosis for liver fibrosis. Methods. Differential expression of five selected miRNAs (hsa-mir-1225-3p, hsa-mir-1238, hsa-miR-3162-3P, hsa-miR-4721, and hsa-miR-H7) was verified by qRT-PCR in the plasma of 83 patients and 20 healthy controls. The relative expression of these miRNAs was analyzed in different groups to screen target miRNA. A logistic regression analysis was performed to assess factors associated with fibrosis progression. The receiver operating characteristic (ROC) curve and discriminant analyses validated the ability of these predicted variables to discriminate the nonsignificant liver fibrosis group from the significant liver fibrosis group. Furthermore, the established models were compared with other prediction models to evaluate the diagnostic efficiency. Results. These five tested miRNAs all had signature correlations with hepatic fibrotic level ( p < 0.05 ), and the upregulation trends were consistent with miRNA microarray analysis previously. The multivariate logistic regression analysis identified that a model of five miRNAs (miR-5) had a high diagnostic accuracy in discrimination of different stages of liver fibrosis. The ROC showed that the miR-5 has excellent value in diagnosis of fibrosis, even better than the Forns score, FIB-4, S index, and APRI. GO functions of different miRNAs mainly involved in various biological processes were markedly involved in HBV and revealed signaling pathways dysregulated in liver fibrosis of CHB patients. Conclusions. It was validated that the combination of these five miRNAs was a new set of promising molecular diagnostic markers for liver fibrosis. The diagnosis model (miR-5) can distinguish significant and nonsignificant liver fibrosis with high sensitivity and specificity.

The MiR-320 Family Is Strongly Downregulated in Patients with COVID-19 Induced Severe Respiratory Failure

“…Beside miR-320, there are many other miRNAs that were strongly deregulated in the patient populations. Of the most upregulated miRNAs, miR-374a-3p and miR-15a-3p are involved in acute kidney and neuroinflammation, respectively, whereas mir-4721 was proposed as one of the miRNA molecular diagnostic markers for liver fibrosis in patients with chronic hepatitis B [ 36 , 37 , 38 ]. Of the most downregulated miRNAs, miR-4747-3p was found upregulated in Alzheimer’s Disease and hsa-miR-4429 was suggested as a potential diagnostic biomarker for biliary atresia [ 39 , 40 ].…”

Identification of miRNA-target gene regulatory networks in liver fibrosis based on bioinformatics analysis

“…In addition, miR-150-5p expression was generally positively correlated with fibrosis severity in rats with carbon tetrachloride-induced liver fibrosis ( Chen et al, 2020b ). On the other hand, in chronic HBV-infected patients, miR-3162-3p expression was higher in the serum of individuals with significant liver fibrosis than those with nonsignificant liver fibrosis ( Zhang et al, 2021 ). In addition to these aforementioned miRNAs and somewhat elusive information, 11 out of 13 miRNAs were shown to be involved in liver cirrhosis for the first time with bioinformatics analysis, and the expression of 7 miRNAs was proved to undergo significant changes in LX2 cells challenged with TGF- β 1 in vitro .…”

Role of noncoding RNAs in liver fibrosis

“…Similarly, Azar et al [ 65 ] constructed a miRNA regulatory network using bioinformatics tools and identified five upregulated miRNAs (miR-21-5p, miR-222-3p, miR-221-3p, miR-181b-5p, and miR-17-5p) that targeted tissue inhibitor of metalloproteinase 3 in activated HSCs, and these results have been verified in a mouse model of liver fibrosis. Zhang et al [ 66 ] performed a logistic regression analysis to show that miR-1225-3p, miR-1238, miR-3162-3p, miR-4721, and miR-H7 could distinguish, with high sensitivity and specificity, nonsignificant fibrosis from significant fibrosis in chronic hepatitis B (CHB) patients. Some researchers screened miRNAs in serum from HCV-related liver fibrosis patients and found that miR-484 was significantly downregulated in advanced liver fibrosis compared to early liver fibrosis and liver cancer[ 67 ], which indicates that miR-484 may be used as a biomarker for staging liver fibrosis in patients with HCV.…”