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Clinical and Translational Oncology

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01-09-2015 | Review Article

Identification of circulating MicroRNAs as novel potential biomarkers for hepatocellular carcinoma detection: a systematic review and meta-analysis

Authors: G. Li, Q. Shen, C. Li, D. Li, J. Chen, M. He

Published in: Clinical and Translational Oncology | Issue 9/2015

Abstract

Background

MicroRNAs (miRNAs) in body fluids such as serum and plasma can be stably detected and used as potential biomarkers in hepatocellular carcinoma (HCC) diagnosis.

Objective

To systematically evaluate circulating miRNAs from HCC expression profiling studies and to determine miRNA biomarkers for HCC detection.

Methods

A systematic review and meta-analysis of published studies were carried out for comparing the circulating miRNA expressions between HCC patients and healthy people, hepatitis, or cirrhosis patients. A miRNA ranking system that considered the number of comparisons in agreement and total number of samples was used. Then the summary receiver-operating characteristic curve (sROC) results of the top miRNAs were combined to further evaluate their diagnostic value using Meta-disc 1.4.

Results

In the 17 included studies, three circulating miRNAs (miR-21, miR-122, and miR-223) were repeatedly reported three times or more in both HCC patients vs. healthy controls and vs. other hepatitis or cirrhosis patients. In further analysis, the area under curve (AUC) of sROC for miR-21, miR-122 and miR-223 in discriminating HCC patients from healthy people are 0.9293, 0.8128, and 0.8597, respectively.

Conclusions

Circulating miR-21 has highest level of diagnostic efficiency among three miRNAs candidate biomarkers (miR-21, miR-122, and miR-223) for detection of HCC.

Venook AP, Papandreou C, Furuse J, de Guevara LL. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist. 2010;15(Suppl 4):5–13. doi:10.1634/theoncologist.2010-S4-05.PubMedCrossRef

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90. doi:10.3322/caac.20107.PubMedCrossRef

Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379(9822):1245–55. doi:10.1016/s0140-6736(11)61347-0.PubMedCrossRef

Behne T, Copur MS. Biomarkers for hepatocellular carcinoma. Int J Hepatol. 2012;2012:859076. doi:10.1155/2012/859076.PubMedCentralPubMedCrossRef

Masuzaki R, Karp SJ, Omata M. New serum markers of hepatocellular carcinoma. Semin Oncol. 2012;39(4):434–9. doi:10.1053/j.seminoncol.2012.05.009.PubMedCrossRef

Ba MC, Long H, Tang YQ, Cui SZ. GP73 expression and its significance in the diagnosis of hepatocellular carcinoma: a review. Int J Clin Exp Pathol. 2012;5(9):874–81.PubMedCentralPubMed

Du Y, Liu M, Gao J, Li Z. Aberrant microRNAs expression patterns in pancreatic cancer and their clinical translation. Cancer Biother Radiopharm. 2013;28(5):361–9. doi:10.1089/cbr.2012.1389.PubMedCrossRef

Costello E, Greenhalf W, Neoptolemos JP. New biomarkers and targets in pancreatic cancer and their application to treatment. Nat Rev Gastroenterol Hepatol. 2012;9(8):435–44. doi:10.1038/nrgastro.2012.119.PubMedCrossRef

Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005;123(4):631–40. doi:10.1016/j.cell.2005.10.022.PubMedCrossRef

10.

Yates LA, Norbury CJ, Gilbert RJ. The long and short of microRNA. Cell. 2013;153(3):516–9. doi:10.1016/j.cell.2013.04.003.PubMedCrossRef

11.

Blanco-Calvo M, Calvo L, Figueroa A, Haz-Conde M, Anton-Aparicio L, Valladares-Ayerbes M. Circulating microRNAs: molecular microsensors in gastrointestinal cancer. Sensors Basel Switz. 2012;12(7):9349–62. doi:10.3390/s120709349.CrossRef

12.

Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105(30):10513–8. doi:10.1073/pnas.0804549105.PubMedCentralPubMedCrossRef

13.

Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141(5):672–5. doi:10.1111/j.1365-2141.2008.07077.x.PubMedCrossRef

14.

Griffith OL, Melck A, Jones SJ, Wiseman SM. Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(31):5043–51. doi:10.1200/jco.2006.06.7330.CrossRef

15.

Chan SK, Griffith OL, Tai IT, Jones SJ. Meta-analysis of colorectal cancer gene expression profiling studies identifies consistently reported candidate biomarkers. Cancer Epidemiol Biomark Prevent A Public Am Assoc Cancer Res Cospon Am Soc Prevent Oncol. 2008;17(3):543–52. doi:10.1158/1055-9965.epi-07-2615.CrossRef

16.

Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25. doi:10.1186/1471-2288-3-25.PubMedCentralPubMedCrossRef

17.

Littenberg B, Moses LE. Estimating diagnostic accuracy from multiple conflicting reports: a new meta-analytic method. Med Dec Making An Int J Soc Med Dec Making. 1993;13(4):313–21.CrossRef

18.

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ Clin Res Ed. 1997;315(7109):629–34.CrossRef

19.

Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions. Cochrane Collaboration and John Wiley: Cochrane Handbook for Systematic Reviews of Interventions; 2008.CrossRef

20.

Abdalla MA, Haj-Ahmad Y. Promising Candidate Urinary MicroRNA Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients. J Cancer. 2012;3:19–31.PubMedCentralPubMedCrossRef

21.

Bihrer V, Waidmann O, Friedrich-Rust M, Forestier N, Susser S, Haupenthal J, et al. Serum microRNA-21 as marker for necroinflammation in hepatitis C patients with and without hepatocellular carcinoma. PLoS ONE. 2011;6(10):e26971. doi:10.1371/journal.pone.0026971.PubMedCentralPubMedCrossRef

22.

Fu Y, Wei X, Tang C, Li J, Liu R, Shen A, et al. Circulating microRNA-101 as a potential biomarker for hepatitis B virus-related hepatocellular carcinoma. Oncol Lett. 2013;6(6):1811–5. doi:10.3892/ol.2013.1638.PubMedCentralPubMed

23.

Giray BG, Emekdas G, Tezcan S, Ulger M, Serin MS, Sezgin O, et al. Profiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma. Mol Biol Rep. 2014;. doi:10.1007/s11033-014-3322-3.PubMed

24.

Gui J, Tian Y, Wen X, Zhang W, Zhang P, Gao J, et al. Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies. Clin Sci Lond. 2011;120(5):183–93. doi:10.1042/cs20100297.PubMedCentralPubMedCrossRef

25.

Koberle V, Kronenberger B, Pleli T, Trojan J, Imelmann E, Peveling-Oberhag J, et al. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer. 2013;49(16):3442–9. doi:10.1016/j.ejca.2013.06.002.PubMedCrossRef

26.

Li J, Wang Y, Yu W, Chen J, Luo J. Expression of serum miR-221 in human hepatocellular carcinoma and its prognostic significance. Biochem Biophys Res Commun. 2011;406(1):70–3. doi:10.1016/j.bbrc.2011.01.111.PubMedCrossRef

27.

Li L, Guo Z, Wang J, Mao Y, Gao Q. Serum miR-18a: a potential marker for hepatitis B virus-related hepatocellular carcinoma screening. Dig Dis Sci. 2012;57(11):2910–6. doi:10.1007/s10620-012-2317-y.PubMedCrossRef

28.

Li LM, Hu ZB, Zhou ZX, Chen X, Liu FY, Zhang JF, et al. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res. 2010;70(23):9798–807. doi:10.1158/0008-5472.can-10-1001.PubMedCrossRef

29.

Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, et al. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012;2(2):e000825. doi:10.1136/bmjopen-2012-000825.PubMedCentralPubMedCrossRef

30.

Qi P, Cheng SQ, Wang H, Li N, Chen YF, Gao CF. Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS One. 2011;6(12):e28486. doi:10.1371/journal.pone.0028486.PubMedCentralPubMedCrossRef

31.

Qu KZ, Zhang K, Li H, Afdhal NH, Albitar M. Circulating microRNAs as biomarkers for hepatocellular carcinoma. J Clin Gastroenterol. 2011;45(4):355–60. doi:10.1097/MCG.0b013e3181f18ac2.PubMedCrossRef

32.

Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, Marubashi S, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol. 2012;56(1):167–75. doi:10.1016/j.jhep.2011.04.026.PubMedCrossRef

33.

Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50(2):136–42. doi:10.1002/mc.20712.PubMedCrossRef

34.

Zhang ZJ, Ge SX, Wang XM, Yuan Q, Yan Q, Ye HM, et al. Serum miR-483-5p as a potential biomarker to detect hepatocellular carcinoma. Hep Intl. 2013;7(1):199–207. doi:10.1007/s12072-012-9341-z.CrossRef

35.

Zheng JJ, Yu FJ, Dong PH, Bai YH, Chen BC. Expression of miRNA-29b and its clinical significances in primary hepatic carcinoma. Zhonghua Yi Xue Za Zhi. 2013;93(12):888–91.PubMed

36.

Zhou J, Yu L, Gao X, Hu J, Wang J, Dai Z, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(36):4781–8. doi:10.1200/jco.2011.38.2697.CrossRef

37.

Hu QY, Jiang H, Su J, Jia YQ. MicroRNAs as biomarkers for hepatocellular carcinoma: a diagnostic meta-analysis. Clin Lab. 2013;59(9–10):1113–20.PubMed

38.

Yang Y, Zhu R. Diagnostic value of circulating microRNAs for hepatocellular carcinoma. Mol Biol Rep. 2014;. doi:10.1007/s11033-014-3578-7.

39.

Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647–58. doi:10.1053/j.gastro.2007.05.022.PubMedCentralPubMedCrossRef

40.

Mar-Aguilar F, Mendoza-Ramirez JA, Malagon-Santiago I, Espino-Silva PK, Santuario-Facio SK, Ruiz-Flores P, et al. Serum circulating microRNA profiling for identification of potential breast cancer biomarkers. Dis Markers. 2013;34(3):163–9. doi:10.3233/dma-120957.PubMedCentralPubMedCrossRef

41.

Si H, Sun X, Chen Y, Cao Y, Chen S, Wang H, et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol. 2013;139(2):223–9. doi:10.1007/s00432-012-1315-y.PubMedCentralPubMedCrossRef

42.

Shen J, Todd NW, Zhang H, Yu L, Lingxiao X, Mei Y, et al. Plasma microRNAs as potential biomarkers for non-small-cell lung cancer. Lab Invest A J Tech Method Pathol. 2011;91(4):579–87. doi:10.1038/labinvest.2010.194.CrossRef

43.

Wei J, Gao W, Zhu CJ, Liu YQ, Mei Z, Cheng T, et al. Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer. Chin J Cancer. 2011;30(6):407–14.PubMedCentralPubMedCrossRef

44.

Kanaan Z, Rai SN, Eichenberger MR, Roberts H, Keskey B, Pan J, et al. Plasma miR-21: a potential diagnostic marker of colorectal cancer. Ann Surg. 2012;256(3):544–51. doi:10.1097/SLA.0b013e318265bd6f.PubMedCrossRef

45.

Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27(15):2128–36. doi:10.1038/sj.onc.1210856.PubMedCrossRef

46.

Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem. 2008;283(2):1026–33. doi:10.1074/jbc.M707224200.PubMedCrossRef

47.

Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 2007;282(19):14328–36. doi:10.1074/jbc.M611393200.PubMedCrossRef

48.

ElHefnawi M, Soliman B, Abu-Shahba N, Amer M. An integrative meta-analysis of microRNAs in hepatocellular carcinoma. Genom Proteom Bioinform. 2013;11(6):354–67. doi:10.1016/j.gpb.2013.05.007.CrossRef

49.

Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene. 2007;26(19):2799–803. doi:10.1038/sj.onc.1210083.PubMedCrossRef

50.

Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65(14):6029–33. doi:10.1158/0008-5472.can-05-0137.PubMedCrossRef

51.

Yao Q, Xu H, Zhang QQ, Zhou H, Qu LH. MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells. Biochem Biophys Res Commun. 2009;388(3):539–42. doi:10.1016/j.bbrc.2009.08.044.PubMedCrossRef

52.

Lou Y, Yang X, Wang F, Cui Z, Huang Y. MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Int J Mol Med. 2010;26(6):819–27.PubMedCrossRef

53.

Li T, Li D, Sha J, Sun P, Huang Y. MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun. 2009;383(3):280–5. doi:10.1016/j.bbrc.2009.03.077.PubMedCrossRef

54.

Fassan M, Pizzi M, Giacomelli L, Mescoli C, Ludwig K, Pucciarelli S, et al. PDCD4 nuclear loss inversely correlates with miR-21 levels in colon carcinogenesis. Virchows Archiv An Int J Pathol. 2011;458(4):413–9. doi:10.1007/s00428-011-1046-5.CrossRef

55.

Wang P, Zou F, Zhang X, Li H, Dulak A, Tomko RJ Jr, et al. microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells. Cancer Res. 2009;69(20):8157–65. doi:10.1158/0008-5472.can-09-1996.PubMedCentralPubMedCrossRef

56.

Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA. 2011;108(12):5003–8. doi:10.1073/pnas.1019055108.PubMedCentralPubMedCrossRef

57.

Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011;13(4):423–33. doi:10.1038/ncb2210.PubMedCentralPubMedCrossRef

58.

McDonald JS, Milosevic D, Reddi HV, Grebe SK, Algeciras-Schimnich A. Analysis of circulating microRNA: preanalytical and analytical challenges. Clin Chem. 2011;57(6):833–40. doi:10.1373/clinchem.2010.157198.PubMedCrossRef

Title: Identification of circulating MicroRNAs as novel potential biomarkers for hepatocellular carcinoma detection: a systematic review and meta-analysis
Authors: G. Li
Q. Shen
C. Li
D. Li
J. Chen
M. He
Publication date: 01-09-2015
Publisher: Springer Milan
Published in: Clinical and Translational Oncology / Issue 9/2015
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-015-1294-y

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