scholarly journals Role of circulating microRNA-21 and microRNA-215 in the diagnosis of hepatitis C related hepatocellular carcinoma

2021 ◽  
Vol 15 (07) ◽  
pp. 997-1003
Author(s):  
Zeinab Sayed Abdelkhalek ◽  
Mohamed Shehata Abdalla ◽  
Mona Mohamed Fathy ◽  
Tamer Mahmoud Elbaz ◽  
Ashraf Omar Abdelaziz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Area Under The Curve ◽  
Expression Level ◽  
Receiver Operating Curve ◽  
Circulating Microrna ◽  
Stem Loop ◽  
Non Invasive ◽  
Reverse Transcription Pcr

Introduction: Several micro ribonucleic acids (miRNAs) are deregulated in hepatocellular carcinoma (HCC). Others are linked to clinical pathological features of HCC. The goal of this study was to investigate whether miRNA-21 and miRNA-215 gene expression could be used as a non-invasive diagnostic tool to diagnose HCC. Methodology: The gene expression of mature miRNA -21 and miRNA -215 in serum was analysed retrospectively using singleplex TaqMan two-step stem-loop quantitative real-time reverse-transcription PCR in 40 patients with HCC, 40 with chronic hepatitis C virus (HCV) with cirrhosis and 40 apparently healthy controls. Results: Expression of miRNA -21 was significantly more down regulated in patients with HCC than in those with non-cirrhotic HCV (P = 0.007; odds ratio = 5; 95% confidence interval 1.6–15.4). The receiver operating curve analysis of the ability of miRNA-21 expression to discriminate between HCC and non-cirrhotic HCV revealed an area under the curve of 0.712 with 70% sensitivity and 68% specificity at a cut-off of ≤ 1.4468. Thus, the expression level of miRNA -21 could discriminate HCC from non-cirrhotic HCV. Significant positive correlation was observed between expression levels of microRNA-21 and miRNA -215 (r = 0.783, p < 0.001), but no association was observed between expression level of miR-215 and HCC or chronic HCV (p = 0.474). Conclusions: MiRNA-21 may be a useful, non-invasive tool for diagnosing HCC. Non-cirrhotic HCV patients have five times the risk of developing HCC when the miRNA -21 level ≤ 1.4468.

scholarly journals Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma

2019 ◽  
Vol 20 (4) ◽  
pp. 864 ◽  
Author(s):  
Anna Weis ◽  
Louise Marquart ◽  
Diego Calvopina ◽  
Berit Genz ◽  
Grant Ramm ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Area Under The Curve ◽  
Preliminary Evidence ◽  
Differentially Expressed ◽  
Mild Disease ◽  
Qrt Pcr ◽  
Reverse Transcription Pcr ◽  
Serum Microrna ◽  
Serum Micrornas

Early diagnosis of cirrhosis and hepatocellular carcinoma (HCC) due to chronic Hepatitis C (CHC) remain clinical priorities. In this pilot study, we assessed serum microRNA (miRNA) expression to distinguish cirrhosis and HCC, alone and in combination with the aminotransferase-to-platelet ratio (APRI), Fibrosis 4 (FIB-4), and alpha-fetoprotein (AFP). Sixty CHC patients were subdivided into 3 cohorts: Mild disease (fibrosis stage F0-2; n = 20); cirrhosis (n = 20); and cirrhosis with HCC (n = 20). Circulating miRNA signatures were determined using a liver-specific real-time quantitative reverse transcription PCR (qRT-PCR) microarray assessing 372 miRNAs simultaneously. Differentially-expressed miRNA candidates were independently validated using qRT-PCR. Serum miRNA-409-3p was increased in cirrhosis versus mild disease. In HCC versus cirrhosis, miRNA-486-5p was increased, whereas miRNA-122-5p and miRNA-151a-5p were decreased. A logistic regression model-generated panel, consisting of miRNA-122-5p + miRNA-409-3p, distinguished cirrhosis from mild disease (area under the curve, AUC = 0.80; sensitivity = 85%, specificity = 70%; p < 0.001). When combined with FIB-4 or APRI, performance was improved with AUC = 0.89 (p < 0.001) and 0.87 (p < 0.001), respectively. A panel consisting of miRNA-122-5p + miRNA-486-5p + miRNA-142-3p distinguished HCC from cirrhosis (AUC = 0.94; sensitivity = 80%, specificity = 95%; p < 0.001), outperforming AFP (AUC = 0.64, p = 0.065). Serum miRNAs are differentially expressed across the spectrum of disease severity in CHC. MicroRNAs have great potential as diagnostic biomarkers in CHC, particularly in HCC where they outperform the only currently-used biomarker, AFP.

Effect of 5'-fluoro-2'-deoxycytidine and sodium butyrate on the genes of the intrinsic apoptotic pathway, p21, p53, cell viability, and apoptosis in human hepatocellular carcinoma cell lines

2021 ◽  
Author(s):  
Masumeh Sanaei ◽  
Fraidoon Kavoosi ◽  
Mohammad Amin Moezzi
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Cell Lines ◽  
Sodium Butyrate ◽  
Cell Apoptosis ◽  
Chromatin Organization ◽  
Expression Level ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway

Backgrounds: Epigenetic regulation such as DNA methylation plays a major role in chromatin organization and gene transcription. Additionally, histone modification is an epigenetic regulator of chromatin structure and influences chromatin organization and gene expression. The relationship between DNA methyltransferase (DNMTs) expression and promoter methylation of the tumor suppressor genes (TSGs) has been reported in various cancers. Previously, the effect of 5-aza-2'-deoxycytidine (5-AZA-CdR), trichostatin A (TSA), and valproic acid (VPA) was shown on various cancers. This study aimed to investigate the effect of 5'-fluoro-2'-deoxycytidine (FdCyd) and sodium butyrate on the genes of the intrinsic apoptotic pathway, p21, p53, cell viability, and apoptosis in human hepatocellular carcinoma SNU449, SNU475, and SNU368 cell lines. Materials and Methods: In this lab trial study, the SNU449, SNU475, and SNU368 cells were cultured and treated with 5'-fluoro-2'-deoxycytidine and sodium butyrate. To determine cell viability, cell apoptosis, and the relative gene expression level, MTT assay, flow cytometry assay, and qRT-PCR were done respectively. Results: 5'-fluoro-2'-deoxycytidine and sodium butyrate changed the expression level of the BAX, BAK, APAF1, Bcl-2, Bcl-xL, p21, and p53 gene (P<0.0001) by which induced cell apoptosis and inhibit cell growth in all three cell lines, SNU449, SNU475, and SNU368.  Conclusion: Both compounds played their roles through the intrinsic apoptotic pathway to induce cell apoptosis.

scholarly journals Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma

Gut ◽  
2018 ◽  
Vol 68 (6) ◽  
pp. 1014-1023 ◽  
Author(s):  
Zhigang Ren ◽  
Ang Li ◽  
Jianwen Jiang ◽  
Lin Zhou ◽  
Zujiang Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gut Microbiome ◽  
Cross Validation ◽  
Area Under The Curve ◽  
Northwest China ◽  
Central China ◽  
Advanced Hcc ◽  
Non Invasive ◽  
Faecal Samples ◽  
Early Hcc

ObjectiveTo characterise gut microbiome in patients with hepatocellular carcinoma (HCC) and evaluate the potential of microbiome as non-invasive biomarkers for HCC.DesignWe collected 486 faecal samples from East China, Central China and Northwest China prospectively and finally 419 samples completed Miseq sequencing. We characterised gut microbiome, identified microbial markers and constructed HCC classifier in 75 early HCC, 40 cirrhosis and 75 healthy controls. We validated the results in 56 controls, 30 early HCC and 45 advanced HCC. We further verified diagnosis potential in 18 HCC from Xinjiang and 80 HCC from Zhengzhou.ResultsFaecal microbial diversity was increased from cirrhosis to early HCC with cirrhosis. Phylum Actinobacteria was increased in early HCC versus cirrhosis. Correspondingly, 13 genera including Gemmiger and Parabacteroides were enriched in early HCC versus cirrhosis. Butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early HCC versus controls. The optimal 30 microbial markers were identified through a fivefold cross-validation on a random forest model and achieved an area under the curve of 80.64% between 75 early HCC and 105 non-HCC samples. Notably, gut microbial markers validated strong diagnosis potential for early HCC and even advanced HCC. Importantly, microbial markers successfully achieved a cross-region validation of HCC from Northwest China and Central China.ConclusionsThis study is the first to characterise gut microbiome in patients with HCC and to report the successful diagnosis model establishment and cross-region validation of microbial markers for HCC. Gut microbiota-targeted biomarkers represent potential non-invasive tools for early diagnosis of HCC.

Non-invasive prediction of hepatocellular carcinoma development using serum fibrosis marker in chronic hepatitis C patients

2013 ◽  
Vol 49 (11) ◽  
pp. 1495-1503 ◽  
Author(s):  
Nobuharu Tamaki ◽  
Masayuki Kurosaki ◽  
Shuya Matsuda ◽  
Masaru Muraoka ◽  
Yutaka Yasui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Non Invasive ◽  
Fibrosis Marker ◽  
Chronic Hepatitis C Patients

scholarly journals A Nomogram Based on Glycolysis-related Gene Expression Profilings Serve as a Novel Prognosis Risk Classifiers for Human Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Lingyu Zhang ◽  
Yu Li ◽  
Yibei Dai ◽  
Danhua Wang ◽  
Xuchu Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Expression Profiles ◽  
Area Under The Curve ◽  
Prognostic Index ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Related Gene ◽  
Metabolic Pattern

Abstract Metabolic pattern reconstruction is an important element in tumor progression. The metabolism of tumor cells is characterized by the abnormal increase of anaerobic glycolysis, regardless of the higher oxygen concentration, resulting in a large accumulation of energy from glucose sources, and contributes to rapid cell proliferation and tumor growth which is further referenced as the Warburg effect. We tried to reconstruct the metabolic pattern in the progression of cancer to screen which genetic changes are specific in cancer cells. A total of 12 common types of solid tumors were enrolled in the prospective study. Gene set enrichment analysis (GSEA) was implemented to analyze 9 glycolysis-related gene sets, which are closely related to the glycolysis process. Univariate and multivariate analyses were used to identify independent prognostic variables for the construction of a nomogram based on clinicopathological characteristics and a glycolysis-related gene prognostic index (GRGPI). The prognostic model based on glycolysis genes has the highest area under the curve (AUC) in LIHC (Liver hepatocellular carcinoma). 8-gene signatures (AURKA, CDK1, CENPA, DEPDC1, HMMR, KIF20A, PFKFB4, STMN1) were related to overall survival (OS) and recurrence-free survival (RFS). Further analysis demonstrates that the prediction model can accurately distinguish between high- and low-risk cancer patients among patients in different clusters in LIHC. A nomogram with a well-fitted calibration curve based on gene expression profiles and clinical characteristics improves discrimination in internal and external cohorts. Furthermore, the altering expression of metabolic genes related to glycolysis may contribute to the reconstruction of the tumor-related microenvironment.

MICRORNA-122 AS A BIOLOGICAL MARKER OF CHRONIC VIRAL HEPATITIS C

2020 ◽  
pp. 72-75
Author(s):  
O. P. Shevchenko-Makarenko ◽  
L. R. Shostakovych-Koretska ◽  
V. E. Dosenko ◽  
T. I. Drevytska
Keyword(s):  
Gene Expression ◽  
Hepatitis C ◽  
Viral Hepatitis ◽  
Biological Marker ◽  
Chronic Viral Hepatitis ◽  
Expression Level ◽  
Healthy Individuals ◽  
Hcv Genotype ◽  
Viral Hepatitis C ◽  
Chronic Viral Hepatitis C

New epigenetic markers are being studied in various countries around the world to diagnose, predict, and treat the patients with chronic viral hepatitis C. Epigenetics is currently studying the hereditary changes in gene expression or phenotype that are not related to the changes in DNA sequence. One field of epigenetics is the expression of RNA that does not encode a protein, namely miRNA, which is a molecule 18−22 nucleotides in length that plays a crucial role in regulating gene expression. Circulating miRNAs are a new genetic material that can be isolated from a patient's blood. The expression level of a particular miRNA has different biological and clinical effects. By means of its determination in various miRNAs it is possible to predict development of diseases. In order to study the baseline expression of miRNA−122 in patients with chronic viral hepatitis C with the first HCV genotype, 74 patients were examined. Diagnosis and monitoring of the patients was performed according to the local protocols and bioethical standards. The level of miRNA−122 expression in patients with chronic viral hepatitis C with the first HCV genotype was established by reverse transcription. Studies show that the level of miRNA−122 expression in the patients with HCV and healthy individuals showed significant variability. The obtained data indicate that the expression level of miRNA−122 in patients is 29 times higher than in healthy individuals at p = 0.0001 (U; Z). This can be an additional biomarker as an index of the presence of chronic viral hepatitis C and can be further used in practice. Therefore, the high level of miRNA−122 expression in subjects (≥ 8.771 rel. units (Log10 miR−122 ≥ 0.939 rel. units)) may be the basis for further screening of patients for HCV infection. The prospects of using this index, which will allow to personalize the diagnosis and treatment tactics for patients, that, in turn, will contribute to the implementation of the WHO global strategy for the elimination of viral hepatitis. Key words: chronic viral hepatitis C, miRNA−122, elimination of viral hepatitis, biological marker.

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