MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma

Table 5 miRNAs patterns in studies enrolling hepatocellular carcinoma patients with hepatitis C virus-related infection

Ref.	Characteristics of the study	miRNAs Up-regulated	miRNAs Down-regulated	Conclusions
Abdalla MA, 2012 Egypt Period: NR	Urine samples collected from: -32 patients with HCC post-HCV infection, -74 patients with chronic HCV infection --12 normal individuals	Up-regulation of: - miR-765, miR200a and miR-610, in the HCC-post HCV group; - miR-335, miR-618, miR-625, miR-532, miR-7 were in both the HCC-post HCV positive group and in the HCV positive group, relative to the control group	Down-regulation of: -miR-765, miR200a and miR-610 in the HCV positive group; - miR-323, miR-449, miR-502d, miR-92b, miR-516-5p and miR-650 in both the HCC-post HCV positive group and in the HCV positive group, relative to the control group	The predictive sensitivity and specificity values of miR-618/650 in tandem for detecting HCC among HCV-positive individuals were 58% and 75%, respectively. These values were higher, compared to the traditional α-feto protein (AFP) level-based detection method
Bihrer V, PLoS One, 2011 Germany Period: NR	Tissue and serum samples obtained from: -CHC: 62; -CHC plus HCC: 29; -Healthy subjects: 29; An -Independent cohort of 47 CHC patients	ND	ND	The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC
El-Garem H, WJG, 2014 Egypt Period: March-June 2012	Serum samples obtained from: -30 with chronic HCV alone (CH); -30 with HCV-related cirrhosis (LC); -30 with HCV-related HCC; -10-age and gender-matched healthy volunteers	Up-regulation of miR-122, miR-221	NR	Serum miR-221 has a strong potential to serve as one of the novel non-invasive biomarkers of HCC
Elhelw DS, Biomedical Reports, 2014 Egypt Period: NR	Serum, liver tissues and peripheral mononuclear cells samples obtained from patients infected with genotype 4-HCV: -72 patients chronically infected with HCV - 22 age-matched controls. The patients classified as: 24 naïve- patients, 11 SVRs pre-treatment, 15 SVRs post-treatment, 12 NRS pre-treatment and 10 NRS post-treatment	miR-181a significantly higher in the serum of naïve patients compared to controls, no difference in miR-181a expression observed in the liver tissues and PBMCs of patients compared to controls up-regulation of miR-181a post-interferon/ribavirin treatment in the serum of SVRs compared to non-responders and treatment-naïve SVR	NR	The up-regulation of miR-181a in the serum of HCV patients as an indication of good prognosis Any decrease during follow-up may be an early marker for progression to HCC
Oksuz Z, Mol Biol Rep, 2015 Turkey Period: NR	Serum samples obtained from: -26 patients with CHC; -30 patients with HCV-related cirrhosis; -8 patients with HCV-positive HCC; -28 patients with control group	Deregulated miR-30a-5p, miR-30c-5p, miR-206, miR302c-3p in CHC Deregulated miR-17-5p, miR-30c-5p, miR-93-5p, miR-130a-3p, miR-223-3p, miR-302c-3p, miR-302c-5p	Deregulated miR-17-5p, miR-30c-5p, miR-223-3p, miR-302c-3p in cirrhosis and HCC	miR-17-5p, miR-30c-5p, miR-223-3p, miR-302c-3p could serve as novel non-invasive biomarkers in the early phases of HCV-related HCC and in the cirrhosis stage of liver disease
Varnholt H Hepatology, 2008 Germany Period: 1995-2007	Tissue samples obtained from: 52 primary liver tumors from 39 patients induced by HCV infection	Increased expression of miR-9, miR-10a, miR-15a, miR-16, miR-299, miR-370 miR-326, miR-let-7g, miR-100, miR-125b in HCC in comparison with normal liver	Decreased expression of miR-198, miR-302b, miR-302b, miR-145, miR-368, miR-218, miR-330, miR-137, miR-147, miR-104, miR-9, miR-106a, miR-204, miR-159a, miR-134, miR-29c, miR-95, miR-199b, miR-185 in HCC in comparison with normal liver	A subset of miRNAs are aberrantly expressed in primary liver tumors, serving both as putative tumor suppressors and as oncogenic regulators
Zhang Y Hepatology, 2012 China Period: NR	Tissue specimens obtained from: -Healthy controls: 7; -NASH:12; -Chronic HCV infection; patients: 34; -HCV-HCC patients:10	Up-regulation of: miRNA-155	NR	HCV-induced miR-155 expression promotes hepatocyte proliferation and tumorigenesis by activating Wnt signaling

BCLC: Barcelona Clinic Liver Cancer staging system; CLD: Chronic liver disease; ER-α: Estrogen receptor-α; FNH: Focal nodular hyperplasia; HCC: Hepatocellular carcinoma; HC: Healthy controls; HCA: Hepatocellular adenoma; LC: Liver cirrhosis; LT: Liver transplantation; NASH: Nonalcoholic steatohepatitis; ND: Not detected; NR: Not reported; NRS: Non-responder; OS: Overall survival; RFS: Recurrence-free survival; SR: Spontaneously recovered; SVRs: Sustained viral responses.