Copyright
©The Author(s) 2016.
World J Gastroenterol. Apr 21, 2016; 22(15): 3907-3936
Published online Apr 21, 2016. doi: 10.3748/wjg.v22.i15.3907
Published online Apr 21, 2016. doi: 10.3748/wjg.v22.i15.3907
Table 1 miRNAs patterns in studies enrolling hepatocellular carcinoma patients with hepatitis B virus-related infection
| References, period and state | Characteristics of the study | miRNAs Up-regulated | miRNAs Down-regulated | Conclusions |
| Bandopadhyay M, BMC Cancer, 2014 India Period: NR | Tissue samples obtained from: -16 healthy subjects -16 patients with advanced liver diseases (HBV positive cirrhosis and HCC) | ND | Decreased miR-21, miR-222 and miR-145 expression in patients with advanced liver diseases and HCC in comparison with healthy individuals | Differential modulation of miRNAs expression by HBx protein |
| Cheong JY, J Korean Med Sci, 2014 Korea Period: NR | Serum samples from: 1439 individuals with either past/ present evidence of HBV infection: -HCC: 417; -LC: 305; -CHB: 313; -SR: 404. | NR | Higher rate of HBV persistence after infection subjects with miR-604 rs2368392 T allele in comparison with miR-604 rs2368392 C allele. Patients with miR-604 T allele may have a higher risk for HBV chronicity Higher rate of the miR-604 T allele in the chronic carrier without HCC | pre-miR-604 rs2368392 polymorphism might confer genetic susceptibility to the occurrence of HCC in HBV related chronic liver disease, and HBV persistence after HBV infection |
| Connolly E, The American Journal of Pathology, 2008 China Period: NR | Human HCC samples and matched non-tumor liver tissue (19 sets) were obtained from surgical resections of anonymous donors | Up-regulation of miR-17-92 (miR-17, miR-19a, miR-20, and miR-92) and miR-21 occurs in precancerous stages of liver disease and in HCC in comparison with normal liver | NR | The combination of assays presented in the present study supports a role for the miR-17-92 polycistron (all six members) or miR-21 in the maintenance of the malignant transformation of hepatocytes |
| Coppola N, PLoS One, 2013 Italy Period: April 2007 - March 2011 | Tissue samples obtained from: twenty-seven consecutive HBsAg/anti-HBe/HBV-DNA-positive Caucasian patients who were naive to nucleos(t)ide analogues and interferon therapy | Higher miR-125a-5p liver concentrations observed in patients with HBV-DNA plasma levels > 103 IU/mL | NR | In HBsAg/anti-HBe-positive patients, the liver miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression |
| Dang YW, Asian Pac J Cancer Prev, 2014 China Period: March 2010 and December 2011 | 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissue 74/89 pairs were obtained from HBV-related HCC samples | NR | Remarkably downregulation of miR-152 expression in HCC compared to that in adjacent hepatic tissues Lower expression was observed in HBV positive group than in the negative one | miR-152 underexpression is associated with hepatocarcinogenesis, acting as a tumor suppressor miRNA, its lack is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis |
| Fan MQ, Journal of Experimental and Clinical Cancer Research, 2013 China Period: 2002 -2007, patients were followed until December 2010 | 100 patients with HCC, undergoing LT 95/100 patients with HBV related cirrhosis Specimens obtained from formalin-fixed paraffin-embedded tissue | NR | Down-regulation of miRNA 20a | miR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Its down-regulation increases the proliferation abilities of HCC cells. miR-20a may represent a novel Potential therapeutic target and biomarker for survival of HCC patients |
| Fu Y, Oncol Letters, 2013 China Period: NR | Serum and tissues (paired tissue specimens from 25 HCC tissues and adjacent noncancerous hepatic tissues (20 HBV-related HCC) were obtained from patients undergoing surgical resection and compared with 20 healthy subjects | miR-101 is upregulated in human HBV-related HCC serum | miR-101 is downregulated in human HBV-related HCC tissues | Serum miR-101 expression was closely associated with tumoral size of HCC-patients and provides a promising biochemical marker of HBV-related HCC |
| Gao P, Hepatology, 2011 Hong Kong Period: NR | Formalin fixed, paraffin embedded materials obtained from: -16 patients with dysplastic nodules -29 HCC nodules from 24 patients | Up-regulation of miR-224 in pre-malignant DNs Up-regulation of miR-10b, miR-21, miR-221, and miR-224 in the small HCCs | Down-regulation of miR-145 and miR-199b in pre-malignant DNs Down-regulation of miR-145 and miR-199b in the small HCCs | miRNA deregulation is an early event and accumulated throughout the various steps of HBV-associated hepatocarcinogenesis. Down-regulation of miR-145 and miR- 199b and up-regulation of miR-224 were frequently observed in pre-malignant DNs and these changes persisted throughout HCC development miR-145 is a candidate tumor suppressive miRNA and may play an important role in HCC development |
| Giray BG, Mol Biol Rep, 2014 Turkey Period: NR | Plasma samples from: -66 HBV-positive patients (CHB: 24, cirrhosis: 22, HCC: 20) -28 healthy controls | mi125b-5p up-regulation in CHB, cirrhosis and HCC in comparison to healthy controls | miR-223-3p down regulation in CHB, cirrhosis and HCC in comparison to healthy controls | miR-125-5 p and miR-223 -3p could be used as novel non-invasive biomarkers of HBV-positive HCC in very early, even at CHB stage of liver disease |
| Gu H, Mol Cell Biochem, 2013 China Period: April 2001 - March 2009 | Tissue samples obtained from 108 patients with HCC, undergoing surgical resection. HBsAg +: 92; HBsAg -: 16 | Up-regulation of miR-372 associated with significant poorer recurrence-free survival and overall survival | NR | miR-372 may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients as well as a promoter of tumorigenicity of HCC and may be a prospective therapeutic target for this malignancy |
| Gui J, Clinical Science, 2011 China Period: November 2008 - January 2010 | Serum samples from: 25 HBV-positive patients (LC: 10, HCC: 15) -10 age-matched healthy controls | Up-regulation of miR-885-5p, miR-574-3p, miR-224, miR-215 and miR-146a in the HCC and LC patients | NR | miR-885-5p is significantly elevated in the sera of patients with liver pathologies miRNAs could serve as novel complementary biomarkers for the detection and assessment of liver pathologies |
| Han Y, PLoS One, 2013 China Period: -September 2009 - June 2010 -October 2009 to September 2011 | Serum samples from: 1,012 healthy controls, 302 HBV natural clearance subjects, 316 ASCs, 316 patients with CHB, 358 HBV-infected patients with LC, and 1,021 HBV-infected patients with HCC Pri-miR-34b/c rs4938723 HBV-HCC patients: 311 HBV-infected subjects without HCC: 210 Pre-miR-196a2 rs11614913 HBV-HCC patients: 255 HBV-infected subjects without HCC: 170 | NR | NR | Association of pri-miR-34b/c rs4938723 with a significant increased risk of HCC, mainly in women No statistically significant association of pre-miR-196a2 rs11614913 with HCC risk. pre-miR-196a2 rs11614913 may enhance the effect of primiR-34b/c rs4938723 in women rs4938723 CC genotype and rs11614913 TC genotype might predispose the host to immune selection of T1674C/G, and G1896A, respectively The rs4938723 effect on HCC risk can be seriously affected by the HBV mutations |
| Hou J, Cancer Cell, 2011 China Period: NR | Tissue samples obtained from 40 HCC patients with CHB | NR | Consistent miR-199a/b-3p decrease in HCC, and its reduction significantly correlates with poor survival of HCC patients | miRNomes of human liver and HCC and contributes to better understanding of the important deregulated miRNAs in HCC and liver diseases |
| Huang J, Hepatology, 2010 China Period: NR | 20 HBV-related HCC tissues and the corresponding nearby noncancerous livers | NR | Down-regulation of miR-152 in human HBV-related HCC Tissues | Tumor suppressive role of miR-152 in the epigenetic aberration of HBV-related HCC and the potential development of miRNA-based targeted approaches for the treatment of HBV-related HCC |
| Huang YH, PLoS One, 2012 China Period: July 1998 - Aug 2004 | Tissue samples obtained from: 228 patients with HCC, 12 with known better and poorer prognosis subjected for the first-step (pilot) study; 6 patients had a RFS time for more than 5 yr (better prognosis) and 6 had rapid relapse within six-month after operation (poorer prognosis) | High expression levels of miR-30c, miR-155, miR-432, miR-15b, and miR-30b associated with shorter RFS High miR-15a, miR-486-3p, and miR-381 expression significantly predicted a longer RFS High expression level of miR-29a, miR-486-3p, and miR-876-5p significantly predicted a longer OS | NR | Significant prognostic miRNA predictors identified through examination of miRNA expression levels in paraneoplastic liver tissues. Functional analysis of miR-155, suggested that the prognostic miRNA predictors identified under this strategy could serve as potential molecular targets for anticancer therapy |
| Jiang R, Clin Cancer Res, 2011 China Period: January 2001 - August 2009 | Liver tissue obtained from: 116 HBV-related HCC patients 48 subjects with benign conditions | up-regulation of miR-22 in male tumor adjacent tissue | NR | Overexpression of miR-22 in male tumor adjacent tissue associated with down-regulated ERa expression, potentially causing the attenuation of the protective effect of estrogen and inducing increased IL-1a expression. These results may explain the high incidence of HBV-associated HCC in the male population |
| Kim HY, J Med Virol, 2014 South Korea Period: NR | Serum samples obtained from: 1439 Korean patients with either past or present HBV infection, -404 control subjects with spontaneous Recovery; -1035 subjects with chronic HBV (313 with chronic hepatitis B, 305 with liver cirrhosis, 417 with HCC) | NR | NR | Protective effect of miR-196a-2 rs12304647 CC genotype against development of HCC in comparison to the AA or AC genotypes in patients with chronic hepatitis and cirrhosis |
| Kwak MS, PLoS One, 2012 South Korea Period: January 2001 - August 2003 | 1439 Korean subjects with past or persistent HBV infection: SR: 404 CHB: 313 chronic LC: 305 HCC : 417 | Micro RNAs-371-372-373 (miRNAs-371-373), originating from the same pri-miRNA transcript, are upregulated in HCC | NR | Among chronic carriers and liver cirrhosis patients, the A allele of rs3859501 and the haplotype pri-miRNAs-371-373_ht2 were more protective to HCC than other genotypes and haplotypes |
| Lan SH, Hepatology, 2014 Taiwan Period: NR | Tissue and specimens, obtained from patients from Taiwan patients with HCC | The level of autophagy was low and inversely Correlated with miR-224 expression only in HBV associated HCC | NR | A noncanonical pathway links autophagy, miR-224, Smad4, and HBV-associated HCC |
| Li J, Biochemical and Biophysical Research Communications, 2011 China Period: NR | Serum samples of HCC were obtained from 46 patient (30 HBsAg positive) The healthy sera were collected from 50 age-matched healthy individuals who serves as normal controls | Serum miR-221, up-regulation in HCC, correlates with tumor size, cirrhosis and tumor stage | NR | Serum miR-221, upregulated in HCC, can provide predictive significance for prognosis of HCC patients |
| Li L, Digestive Diseases and Sciences, 2012 China Period: NR | Serum samples obtained from: HCC: 101 (HBsAg +) CLD and cirrhosis: 30 Healthy controls: 60 | miR-18a significantly up-regulated in HBV- related HCC, chronic hepatitis or cirrhosis than those in healthy Controls | NR | Significant increase of elevated serum miR-18a in the patients of HBV-related HCC. It might serve as a novel noninvasive biomarker to distinguish patients with HBV-related HCC from healthy subjects, and further from those with HBV-related chronic hepatitis or cirrhosis |
| Li LM, Cancer Research, 2010 China Period: September 2007 - July 2008 | Serum samples from: -120 HCC-affected individuals; -135 HBV carriers; -48 HCV carriers; -210 controls | Serum up-regulation of miR-375, miR-92a, miR-10a, miR-223, miR-423, miR-23b/a, miR-342-3p, miR-99a, miR-122a, miR-125b, miR-150, and let-7c. in HBV positive patients with HCC in comparison with healthy controls | NR | The expression profile of serum miRNAs can serve as novel non-invasive biomarkers for the diagnosis of HBV infection and HBV positive HCC. The use of 3 miRNAs: miR-25, miR-375, and let-7f could be used to separate HCC cases from controls, miR-375 alone had high specificity and sensitivity in HCC prediction |
| Li T, Oncology Reports, 2014 China Period: NR | Tissue and plasma obtained from: 31 patients with HBV-related HCC 31 age- and gender-matched CHB patients | Tissue miRNA-21, miRNA-221, miRNA-148b and miRNA-186 over-expression | Tissue miRNA-99a, miRNA-27b, miRNA-378a, miRNA-378e and miRNA-30 down-regulation Tissue and plasma miRNA-139 down-regulation in HCC vs non-HCC patients | miRNA-139 is downregulated in both cancerous tissue and plasma of HCC. The plasma miRNA-139 is a possible diagnostic biomarker for identifying HCC patients while combined with other biomarkers, it is also a prognostic factor for indicating patient survival |
| Li W, Int J Cancer, 2008 China Period: NR | Specimens obtained obtained from: 78 human primary hepatocellular carcinoma (68 HBsAg +) and matched noncancerous liver tissues | 84 miRNAs identified with deregulated expression in tissues from HCC patients. 69/84 miRNAs resulted differentially expressed in normal or non-tumour liver tissue vs cancerous hepatic tissue with 29 miRNAs up-regulated -Noncancerous vs normal liver tissue: 27 miRNAs differentially expressed, with 14 up-regulated in noncancerous liver specimens -HCC vs normal tissue: 55 differentially expressed miRNAs, with 29 up-regulated in HCC tissues | 84 miRNAs identified with deregulated expression in tissues from HCC patients. 69/84 miRNAs resulted differentially expressed in normal or non-tumour liver tissue vs cancerous hepatic tissue with 40 miRNAs down-regulated Noncancerous vs normal liver tissue: 27 miRNAs differentially expressed, with 13 down-regulated in noncancerous liver specimens -HCC vs normal tissue: 55 differentially expressed miRNAs, with 26 down-regulated in HCC tissue | miRNA signature identified as a HCC diagnostic discriminator from both noncancerous and normal liver tissues. This is the first report to identify single miRNA correlated to the HCC prognosis, i.e., miR-125b as a HCC survival predictor |
| Liu AM, BMJ Open, 2012 China Period: 1990-2007 | Serum and Cancerous/non tumors tissue samples collected from: - 96 cirrhotic patients with HCC (84 HBsAg positive) undergoing hepatectomy (exploration phase) -29 hepatitis B carriers, 57 patients with HCC and 30 healthy controls (validation phase) | Exploration phase in resected tumour/adjacent non-tumour tissues: Upregulated miR in the AFP-low (< 400 ng/mL) HCC subgroup: miR-9, -9*, -15b, -21, -34c, -96, -130b, -183, -188, -196b, -216, -224, -301 and -324-5p Upregulated miR in all HCC samples of varying serum AFP levels: miR-15b, -21, -130b, -183, -224 and -301 | Decreased serum miR-224 and miR-301 levels in HCC patients post-surgery in comparison with pre- surgery. Slight reduction of serum miR-15b and miR-130b levels in HCC patients post-surgery in comparison with pre- surgery | The combined miR-15b and miR-130b classifier is a serum biomarker with clinical value (high sensitivity and accuracy) for HCC screening. This classifier also identified early-stage HCC cases that could not be detected by AFP |
| Liu Y, PLoS One, 2012 China Period: January 2006- December-10 Controls screened for the HBV/HCV markers in 2004 and 2009 | Serum samples collected from: - 1300 HBV positive HCC cases, -1344 HBV persistent carriers; - 1344 subjects with HBV natural clearance people These patients were matched to the HCC cases on age and gender | NR | NR | A genetic variant in the promoter region of miR-106b-25 cluster might provide a protective effect against chronic HBV infection but an increased risk for HCC in HBV persistent carriers by affecting the expression of miR-106b-25 cluster A to G base change of rs999885 may have a protective effect on the probability to develop chronic HBV infection, but increased the risk of HCC in HBV persistent carriers |
| Liu Y, J Med Virol, 2014 China Period: April 2008 - November 2011 Newly diagnosed HCC patients included from January 2006 - December 2010 HBV carriers and patients with signs oif past HBv infection, screened from 2004 to 2009 | Samples obtained from: 29 pairs of HCC and adjacent noncancerous liver tissues | NR | In noncancerous liver tissues, subjects with a CA genotype exhibited significantly lower expression level of pri-miR-122 than those carrying the CC genotype. Positive or inverse correlation between the expression levels of pri-miR-122 and mature miR-122 were observed in HCC tissues or oncancerous tissues, respectively | The C to A base change of rs4309483 may alter the expression of miR-122, thus providing protective effect from chronic HBV infection but an increased risk for HCC in HBV carriers |
| Meng FL, Med Oncol, 2014 China Period: January 2009 - December 2011 | Tissue obtained from: 84 patients with HBV-related HCC 31 with CLDs 46 with healthy controls | Tissue miR-24-3p over-expression in HCC in comparison with healthy controls and CLD | NR | The combination of serum miR-24-3p and AFP improves the diagnostic accuracy for HCC prediction compared to each biomarker alone. High serum miR-24-3p level is an independent predictor of overall survival and disease free-survival. In patients with HBV-related HCC |
| Qi, F, PLoS One, 2014 China Period: NR | Serum samples obtained from 331 patients with HBV-related HCC in either intermediate or advanced stage of disease without surgery | NR | NR | miR-106b-25 cluster plays oncogenic roles in cancers through influencing tumor growth, cell survival, and angiogenesis. rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) . rs999885 variant could influence miR-106b-25 expression and the expression levels of miR-106b-25 were significantly higher in AG/GG carriers than that in AA carriers G allele of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese |
| Qi P, PLoS One, 2011 China Period: NR | Study divided into four phases. Serum samples obtained from: (I phase) -10 HBV-positive HCC patients and -10 age- and sex-matched healthy subjects; (II phase) before surgery, sera from another 48 HBV-positive HCC patients, from 48 chronic HBV infection patients without HCC and 24 age- and sex-matched healthy subjects; (III phase) 14 HCC patients before and after surgery, (IV phase) correlation between the expressions of candidate serum miRNAs with clinical parameters of HCC patients | Up-regulation of serum miR-122, miR-222 and miR-223 in HCC patients in comparison with healthy controls | Down-regulation of serum miR-21 in HCC patients in comparison with healthy controls | Serum miR-122 might serve as a novel and potential biomarker for detection of HCC in healthy subjects and it might serve as a novel biomarker for liver injury but not specifically for detection of HCC in chronic HBV infection patients |
| Tan Y, PLoS One, 2014 China Period: August 2010 - June 2013 | Serum samples obtained from: HCC: 261, LC: 133; Healthy controls:173 | up-regulation: miR-190b; miR-141-3p; miR-4532; mir-6127; miR-99b-3p; miR-1228-5p between HCC and healthy controls up-regulation: miR-206, mir-1285-1-p5, miR-10a-5p ,miR-511-5p, miR-433-3p between HCC and cirrhosis groups | Down-regulation: miR-30a-3p; miR-199a-5p ; let-7f-5p ; miR-122-5p ; miR-192-5p; miR-98-5p; miR-574-3p; miR-30e-3p; miR-6852-5p between HCC and healthy controls Down-regulation: miR-100-5p; miR-483-5p, miR-584-5p; miR-28-5p miR-30b-5p; miR-30c-5p ; miR-26a-5p; miR-4454; let-7e-5p; let-7c-5p; miR-4433b-5p between HCC and cirrhosis groups | A serum panel of miRNA with considerable clinical value in HCC diagnosis was identified. miR-206, miR-141-3p, miR-433-3p, miR-1228-5p, miR-199a-5p, miR-122-5p, miR-192-5p, and hsa-miR-26a-5p as potential circulating markers for HCC diagnosis |
| Wei X, Cellular Signalling, 2013 China Period: NR | Serum and tissues (paired tissue specimens from HBV-related HCC tissues and adjacent noncancerous hepatic tissues) | NR | miR-132 is more frequently downregulated in HBV-positive HCCs tumor tissues than in adjacent noncancerous tissues and has a significant inverse correlation with HBx expression in HBV-related HCCs | miR-132 may play a tumor-suppressive role in HBV-related HCC development. Serum miR-132 levels are closely correlated with miR-132 expression levels in tumor tissues. miR-132 may be a promising biochemical marker and may have therapeutic applications in HBV-related HCC |
| Wen Y, Int J Cancer, 2015 China Period (3 phases): December 2010- December 2011 January 2010- December 2012 2004-2005 | Multicenter, three-phase study to screen liver-originated HCC-associated plasma miRNAs in both plasma and tissue samples The training set consisted of 35 HCC cases and 50 cancer-free HBV carriers who were frequency matched for age and sex, whereas the validation set consisted of 32 HCC cases and 32 matched cancer-free HBV carriers | Up-regulation of miR-221, miR-222, miR-31 | Down-regulation of miR-126, and miR-122a miR-223 | miR-223 may represent a potential target in cancer therapy because it regulates Stathmin 1 |
| Xiang Y, Mol Biol Rep, 2012 China Period: December 2009 - February 2011 | Specimens obtained from: -100 patients with HCC (73 HBV positive); -100 patients with CHB; -100 healthy subjects | NR | NR | miRNA 499 polymorphisms is associated with susceptibility in HBV-related HCC in Chinese population. The risk of HCC development is increased in patients with miR-399 C/C was higher in comparison with subjects with miR 499 T/T |
| Xie Y, Cancer Biology and Therapy China Period: NR | Specimens and tissue samples obtained from: -67 HBV-HCC patients, -61 HBV-LC patients, -79 CHB patients, -30 Healthy subjects | Elevated miR-101 levels in the sera and liver tissues of HBV-LC patients and decreased in HBV-HCC patients | NR | Serum miR-101 as a potential biomarker for monitoring the development of HBV-HCC from HBV-LC and the development of HBV-LC from CHB |
| Xing TJ, Genetics and Molecular Research, 2014 China Period: NR | Serum samples obtained from: HCC: 20 patients; LC: 20 patients; CHB: 29 patients; ASC: 20 patients; Healthy controls: 20 | Increased miRNA-122 levels in patients with HCC and CHB vs patients with HC, LC, and ASC | lower miRNA-29 serum levels in LC patients than those in the healthy controls | The elevation in miR-122 was correlated with liver damage in CHB patients and with the pathogenesis of liver cancer in HCC patients. The decrease in miR-29 expression was related to the incidence of liver fibrosis |
| Xu J, Molecular Carcinogenesis, 2011 China Period: NR | Serum samples obtained from: -101 patients with advanced primary HCC (78 HBsAg +), -48 patients with CHB, -89 healthy controls | Higher serum miR-21, miR-122, and miR-223 levels in patients with HCC or CHB, compared with healthy controls | NR | Serum miR-21, miR-122 and miR-223 are elevated in patients with HCC or chronic hepatitis and these miRNAs have strong potential to serve as novel biomarkers for liver injury but not specifically for HCC |
| Zhang H, WJG, 2012 China Period: NR | Serum samples obtained from patients with: -34 CHB, -20 NASH -34 healthy donors Serum samples from 10 CHB patients and 10 controls were subjected to miRNA microarray analysis to obtain serum miRNA profiles | Up-regulation of miR-122, miR-138, miR-638, hsv1-miR-H1, miR-575, miR-572, kshv-miR-K12-3, miR-1915, miR-623, miR-1268, miR-939, miR-498 | Down-regulation of: miR-421, miR-598, miR-155, miR-424, miR-23b, miR-195, miR-487b, miR-224, miR-495, miR-181c, miR-654-3p, let-7e, miR-382, miR-171, miR-128, miR-625, miR-30e1, miR-139-5p, miR-30c, miR-744, miR-374b, miR-376c | Serum levels of miR-122, -572, -575, -638 and -744 are deregulated in patients with CHB or NASH. The levels of these miRNAs may serve as potential biomarkers for liver injury caused by CHB and NASH |
| Zhang T, Neoplasia, 2013 China Period: NR | Samples obtained from cancerous tissues of thirty-three patients with HBV-related HCC and their corresponding nearby nontumorous liver tissues | NR | HBx-mediated downregulation of miR-205 through the induction of miR-205 promoter hypermethylation | HBx is able to inhibit tumor suppressor miR-205. miR-205 may be useful in the treatment of HCC |
| Zhang ZZ, WJG, 2011 China Period: NR | miRNA expression profiles obtained from 78 HCC patients from Gene Expression Omnibus study | 8/ 10 differentially expressed miRNAs common to the AHB infection and HCC datasets were inversely changed, only 3/8 differentially expressed miRNAs common to the chronic HBV infection and HCC datasets exhibited opposite alterations | 8/ 10 differentially expressed miRNAs common to the AHB infection and HCC datasets were inversely changed, only 3/8 differentially expressed miRNAs common to the chronic HBV infection and HCC datasets exhibited opposite alterations | miRNA level is correlated in HBV infection and HCC |
| Zhao Q, PLoS One, 2014 China Period: February 2012 - January 2013 | Serum and cancerous and non-tumors tissue samples obtained from: -66 patients with HBV-related HCC patients -11 hepatic hemangioma Patients | Up-regulation of miR-545/374a cluster in HBV-HCC tissue | NR | The overexpression of miR-545/374a cluster is partially responsible for a poor prognosis, and monitoring sera levels of miR-545/374a may be a useful diagnostic marker for HCC |
| Zhou J, J Clin Oncol, 2011 China Period: August 2008 - June 2010 | 934 blood samples, from healthy subjects patients with CHB, cirrhosis or HCC | High expression levels of miR-192, miR-21, and miR-801 in patients with HCC compared with those in the control group | Low expression levels of miR-122, miR-223, miR-26a, and miR-27a observed in patients with HCC compared with those in the control group | miR panel with considerable clinical value in diagnosing early-stage of HBV-related HCC |
| Zhu HT, PLoS One, 2012 China Period: January 2004 - December 2008 | Tissue obtained from: | Up-regulation in microdissected HCC tissue with early recurrence: miR-29a-5p, miR-27b*, miR-204, miR-29c, miR-10b, miR- | Down-regulation in microdissected HCC tissue with early recurrence: | In the multivariate analyses, miR-29a-5p was identified as an independent factor for tumor recurrence. miR-29a-5p might be a useful marker for the prediction of early tumor recurrence after HCC resection, especially in BCLC 0/A stage HCCs |
| 266 patients, undergoing curative liver resection for HCC 48 patients subdivided into: -group with early recurrence (24) -group without early recurrence (24) 218 patients enrolled into: training (106) and validation (112) cohort | 196b, miR-216a, miR-217, miR-517a, miR-518e, miR-518f, miR-518b, miR-519a, miR-519d, miR-522, miR-486-5p, miR-181c, miR-210, miR-215 Up-regulation in microdissected non-tumorous liver tissue with early recurrence: miR-486-5p, miR-181c, miR-193b*, miR-643, miR-409-3p, miR-424*, miR-139-3p, miR-766 | miR-193b*, miR-643, miR-22, miR-15b, miR-505, miR-107, miR-142-5p, miR-135a, miR-34c-5p, miR-98, miR-483-5p Down-regulation in microdissected non-tumorous liver tissue with early recurrence: miR-210, miR-215, miR-22, miR-409-5p, miR-200a*, miR-10b* |
Table 2 miRNA observed deregulated in studies enrolling hepatocellular carcinoma patients with hepatitis B virus-related infection in at least three papers
| miRNA | Type of deregulation(number of papers) | Type of Sample(number of papers) | Ref. |
| miR-221 | Upregulated (6) | Tissue (5), serum (1) | Gao P, Hepatology, 2011 Li J, Biochemical and Biophysical Research Communications, 2011 Li T, Oncology Reports, 2014 Li W, Int J Cancer, 2008 Wen Y, Int J Cancer, 2015 Zhang ZZ, WJG, 2011 |
| 1miR-21 | Upregulated (5) | Tissue (4), serum (1) | Bandopadhyay M, BMC Cancer, 2014 Connolly E, The American Journal of Pathology, 2008 Gao P, Hepatology, 2011 Li T, Oncology Reports, 2014 Xu J, Molecular Carcinogenesis, 2011 |
| 2miR-222 | Upregulated (4) | Tissue (3), serum (1) | Li W, Int J Cancer, 2008 Qi P, PLoS One, 2011 Zhang ZZ, WJG, 2011 Wen Y, Int J Cancer, 2015 |
| 3miR-122a | Upregulated (4) | Serum (4) | Li LM, Cancer Research, 2010 Qi P, PLoS One, 2011 Xing TJ, Genetics and Molecular Research, 2014 Xu J, Molecular Carcinogenesis, 2011 |
| miR-224 | Upregulated (4) | Tissue (3), serum (1) | Gao P, Hepatology, 2011 Gui J, Clinical Science, 2011 Li W, Int J Cancer, 2008 Zhang ZZ, WJG, 2011 |
| 4miR-101 | Downregulated (4) | Tissue (4) | Fu Y, Oncol Letters, 2013 Li W, Int J Cancer, 2008 Xie Y, Cancer Biology and Therapy, 2014 Zhang ZZ, WJG, 2011 |
| miR-18a | Upregulated (3) | Tissue (2), serum (1) | Li L, Digestive Diseases and Sciences, 2012 Li W, Int J Cancer, 2008 Zhang ZZ, WJG, 2011 |
| miR-223 | Upregulated (3) | Serum (3) | Li LM, Cancer Research, 2010 Qi P, PLoS One, 2011 Xu J, Molecular Carcinogenesis, 2011 |
Table 3 miRNAs patterns in studies enrolling hepatocellular carcinoma patients with hepatitis B virus and hepatitis C virus-related infection
| Ref. | Characteristics of the study | miRNAs Up-regulated | miRNAs Down-regulated | Conclusions |
| Chung GE, Oncol Rep, 2010 Korea Period: 2001-2004 | Tissue samples obtained from twenty-five pairs of primary HCC (18 HBV positive patients, 2 HCV positive subjects, 5 HBV/HCV negative) and adjacent non-tumor liver tissues were evaluated in this study | Up-regulation of miR-15b, miR-105 and miR-339, let-7d, miR-107, miR-103, miR-210, miR-25, let-7a, miR-93, miR-345, miR-30d, miR-423, miR-320 | miR-422b, miR-22, miR-497, miR-195, miR-199a*, miR-199ª, miR-130a | miR-15b expression in HCC tissues may predict a low risk of HCC recurrence. In addition, the modulation of miR-15b expression may be useful as an apoptosis-sensitizing strategy for HCC treatment |
| Cong N, Tumor Biol, 2014 China Period: January 2007 - February 2012 | Serum samples obtained from: -206 patients with HCC -217 controls | NR | NR | The miR-146a GG genotype and G allele carried an increased risk of HCC HBV-positive subjects carrying but not in HCV-infected patients |
| Coulouarn C, Oncogene, 2009 USA Period: NR | Specimens obtained from 64 HCC tissues (18 pts HBsAg +, 13 HCV +, 3 with HBV and HCV coinfection, 30 with different etiologies) and 28 matched non-tumor surrounding liver tissues from patients undergoing partial hepatectomy as treatment for HCC | NR | Down-regulation of miRNA-122 in HCC | miR-122 as a diagnostic and prognostic marker for HCC progression |
| Diaz G, Int J Cancer, 2013 Italy Period: NR | Tissue samples obtained from: -HCV-associated HCC (HCC), -HCC-associated non-tumours cirrhosis (HCC-CIR), -HCV- associated cirrhosis without HCC (CIR), -HBV-associated acute liver failure (ALF), -normal liver tissue surrounding angioma (NL), -normal liver from liver donors (LD) | Up-regulation of: miR 221, miR-224 and miR-224-3p, miR-452, miR-1269 | Down-regulation of: miR-125a-5p , miR-130a, miR-139-5p, miR-139-3p, miR-195, miR-199a-5 and miR-199a-3p, miR-214, miR-424-3p, miR-497 | 18 miRNAs exclusively expressed in HCV-associated HCC and characterized by high specificity and selectivity vs all other liver diseases and healthy conditions were identified Among the 18 HCC-exclusive miRNAs identified in this research, miR-221 and miR-224, miR-199a-5p, miR-195, miR-214, miR-199a-3p, miR-125a-5p, miR-139-5p, miR-130a, miR-199b-3p, miR-139-3p, miR-224-3p and miR-452 were already reported in previous studies miR-497, miRNA-1269 miR-424-3p were never described in previous reports |
| Gramantieri L, Cancer Research, 2007 Italy Period: NR | Tissue obtained from: 60 patients (HBV: 5, HCV: 31, HBV+ HCV: 5, HCV+ pas tHBV: 5, past HBV: 1; HBV + ethanol: 1, HCV + ethanol: 2, ethanol: 3) | Up-regulation of: miR-221 | Down-regulation of : let-7a-1, let-7a2, let-7a3, let-7b, let-7c, let-7d, let-7e, let-7f2, let-7g, miR-122a, miR-124a, miR-130a, miR-132, miR-136, miR-141, miR-142, miR-143, miR-145, miR-146, miR-150, miR-155, miR-181a-1, miR-181a-2, miR-181c, miR-195, miR-199a1-5p, miR-199a2-5p, miR-199b, miR-200b, miR-214, miR-223 | The aberrant expression of a restricted panel of miRNAs could participate in the molecular events leading to HCC development |
| Hao YX, Asian Pac J Cancer Prev, 2013 China Period: January 2010 - April 2012 | Serum samples from: -285 patients with HCC 133 HBsAg-positive 36 anti-HCV positive 8 with coinfection -Residents without HCC who entered the hospital for health check-ups were enrolled into control group Each control was pair-matched by sex and age (± 5 yr) to a patient with HCC | NR | NR | miR-196a2 CC genotype and C allele have an important role in HCC risk in Chinese patients, especially in HBV infection carriers No significant association observed between miR-146aG>C and miR-499A>G genetic polymorphisms and HCC risk |
| Köberle V, Eur J Cancer, 2013 Germany Period: February 2009 - July 2012 | Serum samples obtained from: 195 patients with HCC ( 33 HBV+; 87 HCV +, 14 NASH, 65 Alcohol, 8 Haemochromatosis, 9 Cryptogenic) 54 patients with liver cirrhosis (2 HBV +; 41 HCV +, 0 NASH, 16 Alcohol, 0 Haemochromatosis, 0 Cryptogenic) | Longer OS in patients with higher miR-1 and miR-122 serum levels | Reduced OS in patients with lower miR-1 and miR-122 serum levels | At age-, sex-, tumor stage and treatment-adjusted multivariate Cox regression analysis miR-1 serum levels were independently associated with OS, whereas serum miR-122 was no. t miR-1 may improve the predictive value of classical HCC staging scores |
| Ladeiro Y, Hepatology, 2008 France Period: 1992-2004 | 109 liver samples, collected from 93 patients surgically treated. Analysed cases: HCC: 28, HC: 13, FNH: 5, non-tumor liver samples: 4 Two sets of samples were considered:(first set of samples (n = 50, 16 HBV positive, 9 HCV positive ) and validation set of samples (n = 59, 18 HBV positive, 17 HCV positive) | - miR-96 overexpressed in HBV tumors - miR-21, miR-222, miR-10b overexpression in HCC - miR-224 overexpression in HCC vs benign tumours | -miR-422b, miR-122a down-regulation both in benign and malignant tumors - miR-200c and miR-203 underexpression in benign tumours - low expression of miR-375 in both HCA and HCC mutated for β-catenin | Hepatocellular tumors may have a distinct miRNA expression fingerprint according to malignancy, risk factors, and oncogene/tumor suppressor gene alterations |
| Liu YX, BioMed Research International, 2014 China Period: January 2004 - December 2008 | Tissue obtained from: -207 HCC liver tissue and patients and adjacent noncancerous tissue samples. HBV + : 174 patients; HCV+ : 3 patients | miR-24 up-regulation in HCC tumor tissues relative to adjacent noncancerous tissue samples | NR | High expression of miR-24 could promote AFB1-DNA formation and increase adducts mount. High expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation |
| Liu WH, Gastroenterology, 2009 Taiwan Period: 2002-2006 | Tissue obtained from: -80 HCC patients (40 HBV+ and 40 HCV +), -16 focal nodular hyperplasia cases -7 adenoma cases | Specifically increased miR-18a miRNA in samples from female HCC patients. miR-18a expression in tumor tissues not different from the non-tumoral tissues in either male or female patient FNHs and adenomas | NR | miR-18a prevents translation of ER, potentially blocking the protective effects of oestrogen and promoting the development of HCC in women |
| Lu CY, Genes Chromosomes and Cancer, 2013 Taiwan Period: NR | Tissue and sera obtained from: -41 patients with HCC (19 HBV positive, 11 HCV positive, 2 HBV/HCV positive, 8 HBV/HCV negative and 1 not determined) -8 patients with cirrhosis (6 HBV positive, 2 HCV positive, 1 HBV/HCV positive), -10 Healthy subjects | In 39/41 HCC, the methylation levels of miR-129-2 were significantly increased in tumor tissues compared with adjacent normal tissues miR-129-2 methylation was detectable in plasma samples from HCC patients, but not in plasma samples from healthy individuals or patients with liver cirrhosis | NR | miR-129-2 methylation is highly accurate in distinguishing HCC patients from cirrhosis patients and healthy individuals, implying its potential utility as an early diagnostic marker for HCC |
| Murakami Y, Oncogene, 2006 Japan Period: NR | miR expression profiles in 25 pairs of hepatocellular carcinoma (HCC) and adjacent nontumorous tissue (NT) and nine additional CHB specimens was performed, using a human miRNA microarray HBV +: 6; HCV +: 26 | Major expression of miR-18, precursor miR-18, and miR-224 in HCC vs non-cancerous tissue | Minor expression of miR-199a*, miR-195, miR-199a, miR-200a, and miR-125ª in HCC vs non-cancerous tissue | Higher expression of three miRNAs in the HCC samples vs NT samples, demonstrated lower expression of five miRNAs in the HCC samples vs NT samples |
| Qu KZ, J Clin Gastroenterol, 2011 USA Period: NR | 283 subjects studied: -105 patients with HCC (20 HBV +, 66 HCV +, 1 with coinfection); -107 individuals with CLDs; -71 healthy controls | NR | Significantly lower serum levels of miR-16 and miR-199a in HCC than in CLD patients or control subjects | Measurement of serum levels of miR-16 improves differentiation of HCC from non-HCC CLD. The combination of miR-16, AFP, AFP-L3, and DCP yielded greater sensitivity and specificity for HCC detection than any other single marker or marker combination examined |
| Salvi A, Intern J Oncol, 2012 Italy Period: NR | Tissue specimens obtained from: human HCC samples, corresponding peritumoral and non-tumor samples (resected 1-2 cm from the malignant tumor) 15 HCV + patients, 10 HBV+ patients 4 HBV+/HCV + subjects 7 HBV -/ HCV - patients 5 patients with no available informations (25 cirrhosis, 15 hepatitis, 1 steatosis) | Up-regulation of: miR-21 in HCC tissues vs the corresponding peritumoral tissues, particularly in non-cirrhotic HCC | Down-regulation of: miR-24 and miR-27a in HCCs from cirrhotic liver tissues in comparison to those from non-cirrhotic liver tissues. The downregulation of miR-24 was correlated with poorer prognosis in patients with HBV and HCV virus infections | Differential expression of miRNAs in cirrhotic and non-cirrhotic HCCs, thereby contributing to advances in the discovery and validation of novel molecular biomarkers of HCC progression |
| Sato F, PLoS One, 2011 Japan Period: January 1997 - March 2007 | 73/639 patients with HCC and satisfying enrollment criteria, underwent hepatic resection Patients HBsAg +: 12; Patients HCV +: 51 | Recurrence-related miR in tumor tissues: miR22, miR99a, miR99b, miR100, miR 125a-5p, miR125b, miR129-5p, miR 140-3p, miR145, miR195, miR221, miR378, miR497 | Recurrence-related miRNA in non-tumor tissues: miR18a, miR18b, miR21, miR23a, miR24, miR27a, miR96, miR103, miR 107, miR126, miR142- 3p, miR 148a, miR 191, miR 222, miR362-3p, miR 425, miR378, miR1202, let 7e, let-7f | miRNA profiling can predict HCC recurrence in Milan criteria cases miR-96 in non-tumor tissues is the most strongly associated with HCC recurrence |
| Shigoka M, Pathology International, 2010 Japan Period: NR | Serum and tissue samples obtained from: -22 HCC cases (6 HBV +, 10 HCV +, 6 non-HBV/HCV) -5 pairs of fresh HCC and non-tumorous LCD samples surgically resected from HCC patients -10 healthy subjects | Higher levels of miR-92a expression in HCC sections vs adjacent LC sections | Decreased ratio of miR- 92a to miR-638 in the plasma samples from the HCC patients compared with that from the normal donors | Deregulation of miR-92 expression in cells and plasma could be implicated in the development of HCC |
| Spaniel C, PLoS One, 2013 Japan/USA Period: NR | Tissue samples obtained from: a) Paired tumor and nontumor tissues collected from 26 patients undergoing surgical resection of HCC: -16 with concomitant chronic HCV infection, -10 infected with HBV b) 9 with non-infected ‘normal’ liver tissue collected from patients undergoing resection of metastases of non-hepatic primary cancers | Possible miR-191 increased expression in HBV-associated HCC | Significant reduction of miR-122 abundance in HBV associated HCC in comparison with “normal” liver tissue, but not in liver cancer associated with HCV. Significant differences in miR-122 expression exist in non-tumor tissue, with miR-122 abundance reduced from “normal” in HCV- but not HBV-infected liver | miR-122 abundance varies between HBV- and HCV-related liver HCC as well as in non-tumor tissue |
| Toffanin S, Hoshida Cabellos Gastroenterology, 2011 Italy Period: NR | Tissue samples obtained from: - 89 fresh-frozen HCC samples (surgical resection or LT); - Formalin-fixed paraffin-embedded tissues of 165 HCCs (validation set) caused by HCV, HBV, alcohol, and others Subjects subdivided into: Training set: 79 patients Validation set: 161 patients Training set:, HCV +: 79/79 patients Validation set: HCV +: 74/161; HBV +: 43/161; Alcohol: 12/161; Other: 25/161 | Up-regulation of 23 miRNAs in cluster C2 (miR-517a, miR-517b, miR-517c, miR-520g, miR-520h, miR-519b, miR-519d, miR-516-5p, miR-519a,miR-520c, miR-520b, miR-520f, miR-526b, miR-524, miR-516-1, miR-526b, miR-519e, miR-512-3p, miR-522, miR-526a, miR-518f, miR-518b, and miR-525 Up-regulation of 16 miRNAsin cluster C3 (miR-376a, miR-494, miR-409-3p, miR-376b, miR-377, miR-368, miR-382, miR-369-3p, miR-410, miR-432, miR-154, miR-379, miR-299-5p, miR-431, miR-381, miR-495) | Down-regulation of miR-26a and miR-26b in cluster C2 and C3 | miRNA-based classification of 3 subclasses of HCC is proposed. Among the proliferation class, miR-517a is an oncogenic miRNA, promoting tumor progression A rationale for developing therapies that miRNA 517 for patients with HCC is proposed A hierarchical clustering of miRNA data identified 3 main clusters of HCC: clusters A (32/89), B (29/ 89) and C (28/89). The C cluster divided into 3 sub-clusters with distinct miRNA expression patterns: C1 (15/89), C2 (8/89) and C3 (5/89) |
| Tomimaru Y, J Hepatol, 2011 Japan Period: January2010 - February 2010 | Serum samples obtained from: -10 patients before and after curative resection of HCC (HBV/HCV-: 1, HBV: /3/ HCV+: 6/); -126 patients with HCC, -30 patients with CLD, -50 healthy volunteers | Significantly higher plasma miR-21 level in the HCC patients in comparison with CLD patients and healthy volunteers | Significantly diminished plasma miRNA-21 levels after surgery compared with the pre-operative values | Plasma miRNA-21 level is a promising biochemical marker for HCC |
| Ura S Hepatology, 2009 Japan Period: 1999-2004 | 12 patients with HBV-related HCC 14 patients with HCV-related HCC | NR | Commonly repressed miR in CH-B, CH-C, HCC-B, and HCC-C compared with normal liver: miR-219, miR-320, miR-154, miR-29c; miR-338; miR-26a; miR-126; miR-325 | miRNAs as important mediators of HBV and HCV infection as well as liver disease progression, they could be potential therapeutic target molecules Major miRNAs expression in HCC vs CLD: miR21, miR-98, miR183, miR221, miR222, miR301. Minor miRNAs expression in HCC vs CLD: miR17-3p, miR30a-3p, miR30e, miR92, miR 99a, miR122, miR125b, miR130a, miR139, miR187, miR199a, miR200a, miR200b, miR223, miR326 |
| Zhou B Tumor Biol, 2014 China Period: January 2010 - February 2012 | Serum samples obtained from: -266 patients with HCC -281 Healthy controls | NR | NR | Subjects with miR-146a GG and G allele had an enhanced risk of HCC in comparison with homozygote CC genotype. Individuals with miR-196a2, TT and T allele significantly decreased the risk of HCC in comparison with CC genotype. miR-196a2C>T polymorphisms associated with a decreased risk of HBV-related HCC, but not in HCV-related HCC cases |
Table 4 miRNA observed deregulated in studies enrolling hepatocellular carcinoma patients with hepatitis B virus and hepatitis C virus-related infection in at least three papers
| miRNA | Type of deregulation (number of papers) | Type of Sample (number of papers) | Ref. |
| miR-130a | Downregulated (4) | Tissue (4) | Gramantieri L, Cancer Research, 2007 Diaz G, Int J Cancer, 2013 Chung GE, Oncol Rep, 2010 Oksuz Z, Mol Biol Rep, 2015 |
| miR-21 | Upregulated (3) | Tissue (2), serum (1) | Ladeiro Y, Hepatology, 2008 Salvi A, Intern J Oncol, 2012 Tomimaru Y, J Hepatol, 2011 |
| miR-224 | Upregulated (3) | Tissue (3) | Diaz G, Int J Cancer, 2013 Ladeiro Y, Hepatology, 2008 Murakami Y, Oncogene, 2006 |
| miR-195 | Downregulated (3) | Tissue (3) | Gramantieri L, Cancer Research, 2007 Diaz G, Int J Cancer, 2013 Chung GE, Oncol Rep, 2010 |
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 |
- Citation: Fiorino S, Bacchi-Reggiani ML, Visani M, Acquaviva G, Fornelli A, Masetti M, Tura A, Grizzi F, Zanello M, Mastrangelo L, Lombardi R, Di Tommaso L, Bondi A, Sabbatani S, Domanico A, Fabbri C, Leandri P, Pession A, Jovine E, de Biase D. MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma. World J Gastroenterol 2016; 22(15): 3907-3936
- URL: https://www.wjgnet.com/1007-9327/full/v22/i15/3907.htm
- DOI: https://dx.doi.org/10.3748/wjg.v22.i15.3907