Diagnosis and staging of HCV associated fibrosis, cirrhosis and hepatocellular carcinoma with target identification for miR-650, 552-3p, 676-3p, 512-5p and 147b
Affiliations: [a] Biochemistry and Molecular Biology Department, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt | [b] Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt | [c] Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
Correspondence:
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Corresponding authors: Abdullah Ahmed Gibriel, Biochemistry and Molecular Biology Department, Faculty of Pharmacy, The British University in Egypt (BUE), Suez Rd, EL Sherouk City, Cairo Governorate 11837, Egypt. Tel.: +20 227508073; Fax: +20 223809703; E-mail: abdullah.gibriel@bue.edu.eg. Nagwa Ibrahim Shehata, %****␣cbm-34-cbm210456_temp.tex␣Line␣50␣**** Lecturer of Biochemistry, Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr Al Ainy St., Cairo 11562, Egypt. E-mail: nagwa.mahmoud@pharma.cu.edu.eg.
Abstract: BACKGROUND: Chronic HCV infection progresses to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The latter represents the third most common cause for cancer mortality. Currently, there is no reliable non-invasive biomarker for diagnosis of HCV mediated disorders. OBJECTIVE:Profiling expression signature for circulatory miRNAs in the plasma of 167 Egyptian patients (40 healthy, 48 HCV fibrotic, 39 HCV cirrhotic and 40 HCV-HCC cases). METHODS: QRTPCR was used to quantify expression signature for circulatory miRNAs. RESULTS: MiR-676 and miR-650 were powerful in discriminating cirrhotic and late fibrosis from HCC. MiR-650 could distinguish mild (f0-f1) and advanced (f2-f3) fibrosis from HCC cases. MiR-650 and miR-147b could distinguish early fibrosis from healthy controls meanwhile miR-676 and miR-147b could effectively distinguish between mild chronic and (f1-f3) cases from healthy individuals. All studied miRNAs, except miR-512, can differentiate between (f0-f3) cases and healthy controls. Multivariate logistic regression revealed three potential miRNA panels for effective differentiation of HCC, cirrhotic and chronic liver cases. MiR-676-3p and miR-512-5p were significantly correlated in (f1-f3) fibrosis meanwhile miR-676 and miR-512 could differentiate between cirrhosis and (f0-f3) cases. Both miR-650 and miR-512-5p were positively correlated in the cirrhotic group and in (f0-f4) group. Putative targets for investigated miRNAs were also determined. CONCLUSIONS: Investigated miRNAs could assist in staging and diagnosis of HCV associated disorders.
