Plasma specific miRNAs as predictive biomarkers for diagnosis and prognosis of glioma

Journal of Experimental & Clinical Cancer Research

Keliang Xie²  Jinhuan Wang³  Hong Wang³  Wei Jiang³  Ailin Li³  Pengcun Li¹  Qiong Wang³ 

[1] The Graduate School, Tianjin Medical University, 22 Qixiangtai Street, Tianjin, 300070, P. R. China;Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, 300052, P. R. China;Tianjin Neurosurgery Institute, Tianjin Huanhu Hospital, 122 Qixiangtai Street, Tianjin, 300060, P.R. China

关键词: Biomarker;    Plasma;    MicroRNA;    Glioma;   

Others  :  825616
DOI  :  10.1186/1756-9966-31-97

 received in 2012-10-07, accepted in 2012-11-05,  发布年份 2012

【 摘 要 】

Objective

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a poor prognosis. MicroRNAs (miRNAs) are a class of small non-coding RNAs, approximately 21–25 nucleotides in length. Recently, some researchers have demonstrated that plasma miRNAs are sensitive and specific biomarkers of various cancers. The primary aim of the study is to investigate whether miRNAs present in the plasma of GBM patients can be used as diagnostic biomarkers and are associated with glioma classification and clinical treatment.

Materials and Methods

Plasma samples were attained by venipuncture from 50 patients and 10 healthy donors. Plasma levels of miRNAs were determined by real-time quantitative polymerase chain reaction.

Results

The plasma levels of miR-21, miR-128 and miR-342-3p were significantly altered in GBM patients compared to normal controls and could discriminate glioma from healthy controls with high specificity and sensitivity. However, these three miRNAs were not significantly changed in patients with other brain tumors such as meningioma or pituitary adenoma. Furthermore, the plasma levels of these three miRNAs in GBM patients treated by operation and chemo-radiation almost revived to normal levels. Finally, we also demonstrated that miR-128 and miR-342-3p were positively correlated with histopathological grades of glioma.

Conclusions

These findings suggest that plasma specific miRNAs have potential use as novel biomarkers of glioma and may be useful in clinical management for glioma patients.

【 授权许可】

   
2012 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998, 391:806-811.
• [2]Bartel DP: MicroRNAs: genomics, biogenesis, mechanism and function. Cell 2004, 116:281-297.
• [3]Ambros V: The function of animal microRNAs. Nature 2004, 431:350-355.
• [4]Plasterk RH: MicroRNAs in animal development. Cell 2006, 124:877-881.
• [5]Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR: MicroRNA expression profiles classify human cancers. Nature 2005, 435:834-838.
• [6]Esquela-Kerscher A, Slack FJ: Oncomirs: MicroRNAs with a role in cancer. Nat Rev Cancer 2006, 6:255-269.
• [7]Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer 2006, 6:857-866.
• [8]Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008, 105:10513-10518.
• [9]Baraniskin A, Kuhnhenn J, Schlegel U, Maghnouj A, Zöllner H, Schmiegel W, Hahn S, Schroers R: Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. Neuro Oncol 2012, 14:29-33.
• [10]Roth P, Wischhusen J, Happold C, Chandran PA, Hofer S, Eisele G, Weller M, Keller A: A specific miRNA signature in the peripheral blood of glioblastoma patients. J Neurochem 2011, 118:449-457.
• [11]Conti A, Aguennouz M, La Torre D, Tomasello C, Cardali S, Angileri FF, Maio F, Cama A, Germanò A, Vita G, Tomasello F: miR-21 and 221 upregulation and miR-181b downregulation in human grade II-IV astrocytic tumors. J Neurooncol 2009, 93:325-332.
• [12]Chan JA, Krichevsky AM, Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005, 65:6029-6033.
• [13]Ciafrè SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG: Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 2005, 334:1351-1358.
• [14]Xia H, Qi Y, Ng SS, Chen X, Chen S, Fang M, Li D, Zhao Y, Ge R, Li G, Chen Y, He ML, Kung HF, Lai L, Lin MC: MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells. Biochem Biophys Res Commun 2009, 380:205-210.
• [15]Wang JF, Yu ML, Yu G, Bian JJ, Deng XM, Wan XJ, Zhu KM: Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochem Biophys Res Commun 2010, 394:184-188.
• [16]Lee RC, Feinbaum RL, Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993, 75:843-854.
• [17]Cui JG, Zhao Y, Sethi P, Li YY, Mahta A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM: Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation. J Neurooncol 2010, 98:297-304.
• [18]Thery C, Zitvogel L, Amigorena S: Exosomes: composition, biogenesis and function. Nature Rev Immunol 2002, 2:569-579.
• [19]Février B, Raposo G: Exosome: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol 2004, 16:415-421.
• [20]Pan BT, Johnstone RM: Fate of the transferrin receptor during maturation of sheep reticuloocytes in vitro: selective externalization of the receptor. Cell 1983, 33:967-978.
• [21]Booth AM, Fang Y, Fallon JK, Yang JM, Hildreth JE, Gould SJ: Exosomes and HIV gag bud from endosome-like domains of the T cell plasma membrane. J Cell Biol 2006, 172:923-935.
• [22]Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007, 9:654-659.
• [23]Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T: Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 2010, 285:17442-17452.
• [24]Pigati L, Yaddanapudi SC, Iyengar R, Kim DJ, Hearn SA, Danforth D, Hastings ML, Duelli DM: Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One 2010, 5:e13515.
• [25]Skog J, Würdinger T, Van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM, Breakefield XO: Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biool 2008, 10:1470-1476.
• [26]Turchinovich A, Weiz L, Langheinz A, Burwinkel B: Characterization of extracellular circulating microRNA. Nucleic Acids Res 2011, 39:7223-7233.
• [27]Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosova-Agadjanyan EL, Stirewalt DL, Tait JF, Tewari M: Argonaute 2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA 2011, 108:5003-5008.