Global microRNA expression profiling in the liver biopsies of hepatitis B virus–infected patients suggests specific microRNA signatures for viral persistence and hepatocellular injury

Singh, Avishek; Rooge, Sheetalnath; Varshney, Aditi; Vasudevan, Madavan; Bhardwaj, Ankit; Venugopal, Senthil K.; Trehanpati, Nirupama; Kumar, Manoj; Geffers, Robert; Kumar, Vijay; Sarin, Shiv Kumar

doi:10.1002/hep.29690

Cited by 75 publications

(67 citation statements)

References 48 publications

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“…Then five of these miRNAs were selected for qRT‐PCR validation in a larger cohort, and four of them showed similar expression pattern as those revealed by sequencing data, which indicated a low false discovery rate of our sequencing data and supported the credibility of the profile. Among these differentially expressed miRNAs, hsa‐miR‐99b‐3p, ‐451a, ‐15b‐5p, ‐25‐3p, ‐92a‐3p, ‐106b‐3p, ‐1‐3p, and ‐30a‐5p were also differentially expressed in other stages of HBV infection.…”

Section: Discussionmentioning

confidence: 99%

“…HCs, healthy controls; OBI, occult hepatitis B infection discovery rate of our sequencing data and supported the credibility of the profile. Among these differentially expressed miRNAs, hsa-miR-99b-3p,21 -451a, 22 -15b-5p, 23 -25-3p, 24 -92a-3p,24 -106b-3p, 25 -1-3p,26,27 and -30a-5p 28 were also differentially expressed in other stages of HBV infection. Differentially expressed miRNAs in plasma from OBI vs. healthy controls…”

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confidence: 98%

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Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection

Hao

Wang

Xia

et al. 2019

Journal of Medical Virology

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Emerging suggest that microRNAs (miRNAs) play vital roles in the occurrence and development of hepatitis B virus (HBV) infectious disease. However, miRNAs in occult hepatitis B virus infection (OBI), a special stage of HBV infection, remain largely unknown. Herein, we conducted this study to identify differentially expressed miRNAs and then to investigate the potential roles of these miRNAs in OBI. Plasma miRNA expression profiles of three OBI patients and three healthy controls were analyzed with high through‐put miRNA sequencing technology. Altered expression of miRNAs was further confirmed with reverse transcription quantitative polymerase chain reaction (qRT‐PCR). Finally, bioinformatics analysis was conducted to investigate the involved pathways and target genes for these differentially expressed miRNAs. Totally, 32 differentially expressed miRNAs were identified between OBI and healthy controls by miRNA sequencing (fold change ≥ 1.5, P < .1, and counts per million reads ≥ 1), including 16 downregulated and 16 upregulated miRNAs. Differential expression of hsa‐miR‐486‐5p, ‐25‐3p, and ‐92a‐3p and ‐1‐3p was further validated by qRT‐PCR analysis, which was consistent with miRNA sequencing analysis. Moreover, these four miRNAs might distinguish OBI from HCs efficiently. Bioinformatics analyses indicated that the differentially expressed miRNAs were primarily involved in various biological processes related to gene expression and transcription, cell development and metabolism, protein modification and kinase activity regulation, as well as multiple signaling pathways such as PI3K/Akt signaling pathway. This study provided a global view of miRNA expression in plasma from OBI patients. These differentially expressed miRNAs might play important roles in the development of OBI, which provided intriguing insights into the screening and molecular mechanism of OBI.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection

Hao

Wang

Xia

et al. 2019

Journal of Medical Virology

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“…Importantly, the few studies that examined the liver demonstrated that the phenotype and function of intrahepatic immune cells differ considerably to that of their peripheral counterparts . In recent years, an increasing number of viral hepatitis researchers are describing efforts to fill this gap of knowledge, and are in agreement that a better understanding of liver immunology is crucial for the development of new curative antiviral treatment strategies for chronic hepatitis B . Unfortunately, progress in the field of liver immunology is hampered by practical and technical difficulties .…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5] In recent years, an increasing number of viral hepatitis researchers are describing efforts to fill this gap of knowledge, and are in agreement that a better understanding of liver immunology is crucial for the development of new curative antiviral treatment strategies for chronic hepatitis B. 1,[5][6][7] Unfortunately, progress in the field of liver immunology is hampered by practical and technical difficulties. 6 Core liver biopsies are rarely col- Also, with the expanding use of noninvasive tests of liver disease, such as fibroscan, 9,10 rest material from liver biopsies is less frequently available.…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiling of human tissue-resident immune cells: Comparing blood and liver

Boeijen

Oord

Hou

et al. 2018

Journal of Leukocyte Biology

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In this study, we describe a method to reliably characterize intrahepatic leukocyte populations using flow cytometry and next‐generation RNA sequencing on fresh human liver biopsies. Over the last decades, immune responses of viral hepatitis patients, and of other liver diseases, have been incompletely characterized. Most studies include peripheral blood samples only, foregoing the possibility to investigate the site of inflammation directly. Here, we show that with an optimized protocol that combines cell sorting and RNA sequencing, we can perform a side by side comparison of both intrahepatic and peripheral immune cells. Using core liver biopsies from chronic hepatitis B virus patients, we show that the expression levels of IFN‐stimulated genes and leukocyte‐specific genes are markedly different in the liver compartment as compared to the peripheral blood. These observations emphasize the need to sample the liver directly. The variation of gene expression profiles in these chronic hepatitis B patients was considerable, despite the uniform treatment with nucleotide analogs and absence of liver inflammation in these patients. Finally, we show that this method can provide a detailed characterization of previously undetected liver‐specific effects of novel candidate therapeutic compounds.

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“…404 In HBV, increased tissue miRNA-10b-5p expression correlated with increased disease severity (by fibrosis stage). 405 In biopsy-proven NAFLD, however, significant differential expression of miRNA-10b-5p in serum was not observed when compared to healthy control patients, although the trend was towards decreased expression. In that study, however, a negative correlation between serum miRNA-10b-5p levels and the presence of inflammation was observed.…”

Section: Mirna-10a-5p and Mirna-10b-5pmentioning

confidence: 92%

Investigating the potential of circulating microRNAs as non-invasive biomarkers in cirrhosis and hepatocellular carcinoma

Weis¹

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Identification of 5 miRNA candidates (miRNA-10a-5p, miRNA-10b-5p, miRNA101-3p, miRNA 22-3p and miRNA-27b-3p) in the serum of 136 patients with cirrhosis that are differentially expressed according to disease severity in compensated cirrhosis (n=30), cirrhosis with varices (n=30), cirrhosis with ascites ± varices (n=60), and cirrhosis with variceal bleeding (n=16). MiRNA panels were assembled to distinguish patients with specific complications with the following diagnostic performance: • Varices panel (miRNA-10b-5p + miRNA-101-3p) with an AUC of 0.78 (95% CI 0.66-0.90, p<0.001) • Ascites panel (miRNA-10a-5p + miRNA-146a-5p) with an AUC of 0.83 (95% CI 0.75-0.92, p<0.001) • Variceal bleeding panel (miRNA-10a-5p) with an AUC of 0.80 (95% CI 0.65-0.95, p<0.001) • Decompensation panel, grouping ascites and variceal bleeding patients (miRNA-10a-5p, miRNA-146a-5p + miRNA-423-3p) with an AUC of 0.78 (95% CI 0.70-0.86, p<0.001). Combining platelet count < 150 (x10 9 /L) 2 with the miRNA panels improved the performance of the Varices panel and the Ascites panel (with AUCs of 0.84 and AUC of 0.87, respectively). This thesis has identified several differentially-expressed miRNA candidates across a clinically relevant spectrum of CLD and assembled promising panels of miRNAs that warrant further investigation for their diagnostic potential. Preliminary efforts to explore the possible functional roles of 2 candidates in HCC were unrewarding but further studies can build on these findings by optimising experimental conditions, validating identified miRNA candidates, and testing the prognostic potential of validated miRNAs as clinically-useful non-invasive biomarkers.

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Global microRNA expression profiling in the liver biopsies of hepatitis B virus–infected patients suggests specific microRNA signatures for viral persistence and hepatocellular injury

Abstract: miRNA signatures identified in this study corroborate previous findings and provide fresh insight into the understanding of HBV-associated liver diseases which may be helpful in developing early-stage disease diagnostics and targeted therapeutics. (Hepatology 2018;67:1695-1709).

Cited by 75 publications

References 48 publications

Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection

Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection

Gene expression profiling of human tissue-resident immune cells: Comparing blood and liver

Investigating the potential of circulating microRNAs as non-invasive biomarkers in cirrhosis and hepatocellular carcinoma

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