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Investigating circulatory microRNA expression profiles in Egyptian patients with HCV induced hepatocellular carcinoma

Hepatitis C virus (HCV) infection is a serious health challenge affecting over 185 million individuals globally. Egypt has the highest rate for chronic HCV infection worldwide. Recent studies have shown that from 10%-30% of HCV infected individuals would progress to more deteriorating condi...

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Main Author: Al Anany, Amany
Format: Thesis
Published: AUC Knowledge Fountain 2018
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author Al Anany, Amany
author_browse Al Anany, Amany
author_facet Al Anany, Amany
author_sort Al Anany, Amany
collection Thesis
dc_rights_str_mv The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy.
description Hepatitis C virus (HCV) infection is a serious health challenge affecting over 185 million individuals globally. Egypt has the highest rate for chronic HCV infection worldwide. Recent studies have shown that from 10%-30% of HCV infected individuals would progress to more deteriorating conditions such as cirrhosis and/or hepatocellular carcinoma (HCC). Current biomarkers for HCC diagnosis are lacking both sensitivity and specificity. As a result there is demand to develop reliable biomarkers that are sensitive, specific and non-invasive for early diagnosis and rapid intervention of HCC to increase the survival rate of patients. Recently, circulatory miRNAs have drawn great attention as promising non-invasive biomarkers for various diseases. They are highly stable in blood and their expression profiles reflect disease progression and/or drug response status. Besides, a number of miRNAs were found to be commonly dysregulated in HCC. In this study, we investigated mi-RNA expression profile from the plasma of Egyptian patients with chronic hepatitis C, cirrhosis and HCV associated HCC compared with healthy control. We aimed to assess the diagnostic potential of the selected miRNAs to differentiate between healthy, HCV and HCV associated disorders (cirrhosis and HCC). In addition to studying the expression pattern in the different studied stages. Using real time PCR, we compared the levels of circulating mir-122, miR-21 and miR-155 in plasma from healthy control (n=40), cirrhosis (n=39) and HCC (n=40) to CHC (n=37). Synthetic miR-39 was spiked in the samples to be used as a normalizing control for the samples. Plasma miR-122 was significantly up-regulated iii in HCC than in the three other categories (P<0.001). The plasma level of miR-122 in HCC patients was significantly higher than healthy control and cirrhotic patients (P = 0.002 and P<0.001, respectively). The plasma level of miR-21 was significantly upregulated in HCC compared to cirrhotic patients (P=0.03). Although Control and HCC in mir-21 increased by 3.52 and 6 log2 scale respectively, they were in marginal insignificance (p=0.093) that might be due to limited number of samples used in this study. There had been no significant dys-regulation in the expression levels of miR155 between the 4 categories. Receiver operating characteristic curves’ analysis revealed that miR-122 differentiated HCC patients from healthy control with a specificity and sensitivity 57.50% and 65.52% respectively (at a cutoff >1.86). To discriminate cirrhotic patients from HCC subjects, a specificity and sensitivity of 61.54% and 1.43% (at a cutoff> 0.43) were determined. Additionally, analyzing ROC curve indicated that miR-21 differentiated HCC patients from cirrhotic patients with best sensitivity and specificity 72.97% and 50% (at a cutoff >-0.43). In conclusion, plasma miR-122 and miR-21 may be further investigated as potential markers for HCV associated HCC.
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spelling oai:fount.aucegypt.edu:etds-1431 Investigating circulatory microRNA expression profiles in Egyptian patients with HCV induced hepatocellular carcinoma Al Anany, Amany Hepatitis C virus (HCV) infection is a serious health challenge affecting over 185 million individuals globally. Egypt has the highest rate for chronic HCV infection worldwide. Recent studies have shown that from 10%-30% of HCV infected individuals would progress to more deteriorating conditions such as cirrhosis and/or hepatocellular carcinoma (HCC). Current biomarkers for HCC diagnosis are lacking both sensitivity and specificity. As a result there is demand to develop reliable biomarkers that are sensitive, specific and non-invasive for early diagnosis and rapid intervention of HCC to increase the survival rate of patients. Recently, circulatory miRNAs have drawn great attention as promising non-invasive biomarkers for various diseases. They are highly stable in blood and their expression profiles reflect disease progression and/or drug response status. Besides, a number of miRNAs were found to be commonly dysregulated in HCC. In this study, we investigated mi-RNA expression profile from the plasma of Egyptian patients with chronic hepatitis C, cirrhosis and HCV associated HCC compared with healthy control. We aimed to assess the diagnostic potential of the selected miRNAs to differentiate between healthy, HCV and HCV associated disorders (cirrhosis and HCC). In addition to studying the expression pattern in the different studied stages. Using real time PCR, we compared the levels of circulating mir-122, miR-21 and miR-155 in plasma from healthy control (n=40), cirrhosis (n=39) and HCC (n=40) to CHC (n=37). Synthetic miR-39 was spiked in the samples to be used as a normalizing control for the samples. Plasma miR-122 was significantly up-regulated iii in HCC than in the three other categories (P<0.001). The plasma level of miR-122 in HCC patients was significantly higher than healthy control and cirrhotic patients (P = 0.002 and P<0.001, respectively). The plasma level of miR-21 was significantly upregulated in HCC compared to cirrhotic patients (P=0.03). Although Control and HCC in mir-21 increased by 3.52 and 6 log2 scale respectively, they were in marginal insignificance (p=0.093) that might be due to limited number of samples used in this study. There had been no significant dys-regulation in the expression levels of miR155 between the 4 categories. Receiver operating characteristic curves’ analysis revealed that miR-122 differentiated HCC patients from healthy control with a specificity and sensitivity 57.50% and 65.52% respectively (at a cutoff >1.86). To discriminate cirrhotic patients from HCC subjects, a specificity and sensitivity of 61.54% and 1.43% (at a cutoff> 0.43) were determined. Additionally, analyzing ROC curve indicated that miR-21 differentiated HCC patients from cirrhotic patients with best sensitivity and specificity 72.97% and 50% (at a cutoff >-0.43). In conclusion, plasma miR-122 and miR-21 may be further investigated as potential markers for HCV associated HCC. 2018-06-01T07:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/432 https://fount.aucegypt.edu/context/etds/article/1431/viewcontent/Thesis_20final_20draft_205.February.2018.pdf The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. Theses and Dissertations AUC Knowledge Fountain Biomarkers microRNA
spellingShingle Biomarkers
microRNA
Al Anany, Amany
Investigating circulatory microRNA expression profiles in Egyptian patients with HCV induced hepatocellular carcinoma
title Investigating circulatory microRNA expression profiles in Egyptian patients with HCV induced hepatocellular carcinoma
title_full Investigating circulatory microRNA expression profiles in Egyptian patients with HCV induced hepatocellular carcinoma
title_fullStr Investigating circulatory microRNA expression profiles in Egyptian patients with HCV induced hepatocellular carcinoma
title_full_unstemmed Investigating circulatory microRNA expression profiles in Egyptian patients with HCV induced hepatocellular carcinoma
title_short Investigating circulatory microRNA expression profiles in Egyptian patients with HCV induced hepatocellular carcinoma
title_sort investigating circulatory microrna expression profiles in egyptian patients with hcv induced hepatocellular carcinoma
topic Biomarkers
microRNA
url https://fount.aucegypt.edu/etds/432
https://fount.aucegypt.edu/context/etds/article/1431/viewcontent/Thesis_20final_20draft_205.February.2018.pdf
work_keys_str_mv AT alananyamany investigatingcirculatorymicrornaexpressionprofilesinegyptianpatientswithhcvinducedhepatocellularcarcinoma