MicroRNA profiles in serum samples from patients with stable cirrhosis and miRNA-21 as a predictor of transplant-free survival

Amaral, Alex Evangelista do; Rode, Michele Patrícia; Cisilotto, Júlia; Silva, Telma Erotides da; Fischer, Josiane; Matiollo, Camila; Rateke, Elayne Cristina de Morais; Narciso-Schiavon, Janaína Luz; Schiavon, Leonardo Lucca; Creczynski-Pasa, Tânia Beatriz

doi:10.1016/j.phrs.2018.06.019

Cited by 24 publications

(15 citation statements)

References 52 publications

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“…2, shaded yellow) and is significantly associated with the expression of AST, a liver damage marker (Table 2). These results are consistent with previous findings of up-regulation of serum miR-34a-5p in patients with cirrhosis and positive correlation between serum miR-34a-5p and AST level 30 .…”

Section: Discussionsupporting

confidence: 93%

“…Consistent with our observation, circulating levels of miR-122-5p 21 , miR-125b-5p 22 , miR-100-5p 23 , miR-885-5p 29 were also previously reported to be higher in HCC patients compared to normal healthy group. Similarly, circulating levels of miR-122-5p 30 , miR-125b-5p 22 and miR-885-5p 29,30 were also previously reported to be up-regulated in various liver pathologies including CHB and cirrhosis. Circulating miR-148a-3p was elevated in patients undergoing liver transplantation 31 .…”

Section: Discussionmentioning

confidence: 66%

See 1 more Smart Citation

Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma

Jin

Wong

Goh

et al. 2019

Sci Rep

107

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Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3 rd cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 66%

Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma

Jin

Wong

Goh

et al. 2019

Sci Rep

107

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“…Previous studies have evaluated the presence and relevance of circulating miRNAs in liver diseases such as cirrhosis [24,25,28], and hepatocellular carcinoma appearance [21,[29][30][31]. Recently, a study by Cisilotto et al [32] evaluated circulating miRNAs in ACLF and identified miR-25-3p and miR-223-3p as being significantly dysregulated in ACLF patients, however, these results were not confirmed in our study.…”

Section: Discussioncontrasting

confidence: 77%

Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure

et al. 2021

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Background & Aims MicroRNAs (miRNAs) circulate in several body fluids and can be useful biomarkers. The aim of this study was to identify blood-circulating miRNAs associated with cirrhosis progression and acute-on-chronic liver failure (ACLF). Methods Using high-throughput screening of 754 miRNAs, serum samples from 45 patients with compensated cirrhosis, decompensated cirrhosis, or ACLF were compared with those from healthy individuals (n = 15). miRNA levels were correlated with clinical parameters, organ failure, and disease progression and outcome. Dysregulated miRNAs were evaluated in portal and hepatic vein samples (n = 33), liver tissues (n = 17), and peripheral blood mononuclear cells (PBMCs) (n = 16). Results miRNA screening analysis revealed that circulating miRNAs are dysregulated in cirrhosis progression, with 51 miRNAs being differentially expressed among all groups of patients. Unsupervised clustering and principal component analysis indicated that the main differences in miRNA expression occurred at decompensation, showing similar levels in patients with decompensated cirrhosis and those with ACLF. Of 43 selected miRNAs examined for differences among groups, 10 were differentially expressed according to disease progression. Moreover, 20 circulating miRNAs were correlated with model for end-stage liver disease and Child-Pugh scores. Notably, 11 dysregulated miRNAs were associated with kidney or liver failure, encephalopathy, bacterial infection, and poor outcomes. The most severely dysregulated miRNAs ( i.e. miR-146a-5p, miR-26a-5p, and miR-191-5p) were further evaluated in portal and hepatic vein blood and liver tissue, but showed no differences. However, PBMCs from patients with cirrhosis showed significant downregulation of miR-26 and miR-146a, suggesting a extrahepatic origin of some circulating miRNAs. Conclusions This study is a repository of circulating miRNA data following cirrhosis progression and ACLF. Circulating miRNAs were profoundly dysregulated during the progression of chronic liver disease, were associated with failure of several organs and could have prognostic utility. Lay summary Circulating miRNAs are small molecules in the blood that can be used to identify or predict a clinical condition. Our study aimed to identify miRNAs for use as biomarkers in patients with cirrhosis or acute-on-chronic liver failure. Several miRNAs were found to be dysregulated during the progression of disease, and some were also related to organ failure and disease-related outcomes.

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“…In agreement with our findings, reduced serum levels of miR-122, the most abundant miRNA in the liver, and of miR-885-5p have been reported in patients with decompensated compared to those with compensated cirrhosis. (29)(30)(31) Such lower serum levels of these miRNAs in patients with more advanced disease may be secondary to their reduced secretion due to a loss of functional hepatocytes rather than to their increased release from injured hepatocytes seen in earlier stages of liver diseases.…”

Section: Discussionmentioning

confidence: 99%

Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature

Paredes

Manicardi²,

Téllez

et al. 2021

Hepatology Communications

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Noninvasive staging of decompensated cirrhosis is an unmet clinical need. The aims of this study were to characterize and validate a novel microRNA (miRNA) signature to stage decompensated cirrhosis and predict the portal pressure and systolic cardiac response to nonselective beta-blockers (NSBBs). Serum samples from patients with decompensated cirrhosis (n = 36) and healthy controls (n = 36) were tested for a novel signature of five miRNAs (miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p) identified in the secretome of primary human hepatocytes and for three miRNAs (miR-192-5p, miR-34a-5p, and miR-29a-5p) previously discovered as biomarkers of chronic liver disease. All patients had ascites, which was refractory in 18 (50%), and were placed on NSBBs for variceal bleeding prophylaxis. In all patients, serum miRNAs, hepatic venous pressure gradient, and an echocardiogram study were performed before and 1 month after NSBBs. Patients with cirrhosis had lower serum levels of miR-429, miR-885-5p, miR-181b-5p, miR-122-5p, miR-192-5p, and miR-29a-5p (P < 0.05). Baseline serum miR-452-5p and miR-429 levels were lower in NSBB responders (P = 0.006). miR-181b-5p levels were greater in refractory ascites than in diuretic-sensitive ascites (P = 0.008) and correlated with serum creatinine. miR-452-5p and miR-885-5p were inversely correlated with baseline systemic vascular resistance (ρ = −0.46, P = 0.007; and ρ = −0.41, P = 0.01, respectively) and with diminished systolic contractility (ρ = −0.55, P = 0.02; and ρ = −0.55, P = 0.02, respectively) in patients with refractory ascites after NSBBs. Conclusion: Analysis of a miRNA signature in serum discriminates between patients with decompensated cirrhosis who show more severe systemic circulatory dysfunction and compromised systolic function after beta-blockade and those more likely to benefit from NSBBs. (Hepatology Communications 2021;5:309-322). M icroRNAs (miRNAs) are small noncoding RNA molecules (18-25 nucleotides) involved in the posttranscriptional regulation of protein-coding genes controlling many cellular processes. (1) In serum, miRNAs may be bound to circulating proteins or, more frequently, contained within extracellular vesicles (EVs). (2) EVs are nanometric double-membrane structures that envelop miR-NAs and shuttle this biological information from one cell type to another. Because their cargo dynamically

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MicroRNA profiles in serum samples from patients with stable cirrhosis and miRNA-21 as a predictor of transplant-free survival

Cited by 24 publications

References 52 publications

Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma

Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma

Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure

Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature

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