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

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...

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Main Authors: Qingqing Zhang, Qidi Zhang, Binghang Li, Ying Qu, Zhenghong Li, Lungen Lu, Rongzhou Li, Xiaobo Cai
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/6636947
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author Qingqing Zhang
Qidi Zhang
Binghang Li
Ying Qu
Zhenghong Li
Lungen Lu
Rongzhou Li
Xiaobo Cai
author_facet Qingqing Zhang
Qidi Zhang
Binghang Li
Ying Qu
Zhenghong Li
Lungen Lu
Rongzhou Li
Xiaobo Cai
author_sort Qingqing Zhang
collection DOAJ
description 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.
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spelling doaj-art-5e66ea5afbde454789003e95b3783d8e2025-02-03T01:29:21ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/66369476636947The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis BQingqing Zhang0Qidi Zhang1Binghang Li2Ying Qu3Zhenghong Li4Lungen Lu5Rongzhou Li6Xiaobo Cai7Department of Gastroenterology, Ruian People’s Hospital, Wenzhou, Zhejiang Province 325200, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Gastroenterology, Ruian People’s Hospital, Wenzhou, Zhejiang Province 325200, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaBackground 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.http://dx.doi.org/10.1155/2021/6636947
spellingShingle Qingqing Zhang
Qidi Zhang
Binghang Li
Ying Qu
Zhenghong Li
Lungen Lu
Rongzhou Li
Xiaobo Cai
The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B
Mediators of Inflammation
title The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B
title_full The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B
title_fullStr The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B
title_full_unstemmed The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B
title_short The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B
title_sort diagnosis value of a novel model with 5 circulating mirnas for liver fibrosis in patients with chronic hepatitis b
url http://dx.doi.org/10.1155/2021/6636947
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