Serum MicroRNAs as Potential Biomarkers for Early Diagnosis of Hepatitis C Virus-Related Hepatocellular Carcinoma in Egyptian Patients.
Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV)-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis progression to cirrhosis to HCC. We identified a panel of four serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Tarek K
TK
Motawi
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Olfat G
OG
Shaker
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Shohda A
SA
El-Maraghy
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Mahmoud A
MA
Senousy
D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology / Q000821:virology; D055088:Early Detection of Cancer; D005260:Female; D016174:Hepacivirus / Q000472:pathogenicity; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis
D014408:Biomarkers, Tumor; C542542:MIRN146 microRNA, human; C549214:MIRN19A microRNA, human; C546783:MIRN192 microRNA, human; C552722:MIRN195 microRNA, human; D035683:MicroRNAs