Clinical impact of circulating oncogenic MiRNA-221 and MiRNA-222 in glioblastoma multiform

被引:42
作者
Swellam, Menha [1 ,2 ]
El Arab, Lobna Ezz [3 ]
Al-Posttany, Amr S. [4 ]
Said, Samy B. [3 ]
机构
[1] Natl Res Ctr, Biochem Dept, Genet Engn & Biotechnol Res Div, Giza, Egypt
[2] Natl Res Ctr, High Throughput Mol & Genet Lab, Ctr Excellences Adv Sci, El Bohouth St, Giza 12622, Egypt
[3] Ain Shams Univ, Fac Med, Clin Oncol Dept, Cairo, Egypt
[4] Damietta Univ, Chem Dept, Fac Sci, New Damietta, Egypt
关键词
MiRNA; Glioblastoma multiform; Prognosis; Response; EXPRESSION; MICRORNAS;
D O I
10.1007/s11060-019-03256-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background and aim Glioblastoma multiform (GBM); most fatal brain cancer, is incurable with molecular diversity hence identification of molecular targets that contribute to GBM tumorgenesis will be suitable for the development of diagnostic and treatment strategies. Micro-RNAs (miR); small RNA molecules, are stable in blood and play a crucial role in molecular processes in GBM. Thus it was aimed to investigate the clinical role of miR-221 and miR-222 among GBM cases as compared to healthy individuals and illustrate their role in patient's survival. Materials and methods Blood samples were withdrawn from 20 GBM cases before and after treatment, a group of 20 healthy individuals were served as control. For all enrolled samples expression of miR-221 and miR-222 were detected using quantitative PCR (QPCR). Sensitivities, specificities of investigated miRs and their relation with GBM clinical characteristics and patient's outcome were analyzed using Kaplan Meir curve. Results Expression of investigated miR- 221 and -222 were significantly increased in GBM cases as compared to healthy individuals (F = 12.9, at P < 0.001, F = 28.78, at P < 0.0001, respectively) and with absolute specificity for both and 90% sensitivity for miR-221 and 85% for miR-222. Among GBM patients (n = 20), mean expression level miR-221 reported significant increase with elder GBM ( > 60 years) at F = 5.7, P = 0.028, while both miR-221 and -222 showed significant difference in performance status (ECGO) at P = 0.036 and 0.007, patients with primary lesion at P = 0.001 and 0.005, surgically treatment strategy at P < 0.001 and 0.004, respectively. Patients were grouped according to their outcomes into response (complete [CR] or partial [PR]), stable disease[SD] and progressive disease [PD], miR-221 and miR-222 showed increase expression with PD and patients with worse PFS and OS were those with high miRs expression. Conclusion Detection of circulating miR-221 and miR-222 may be used as circulating molecular marker for diagnosis and prediction of outcome for patients with GBM. Further studies with large cohort of samples are encouraged.
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页码:545 / 551
页数:7
相关论文
共 26 条
[1]   Elderly patients with glioblastoma: State of the art [J].
Biau, Julian ;
Dalloz, Pierre ;
Durando, Xavier ;
Hager, Marie-Odile ;
Ouedraogo, Zangbewende Guy ;
Khalil, Toufic ;
Lemaire, Jean-Jacques ;
Chautard, Emmanuel ;
Verrelle, Pierre .
BULLETIN DU CANCER, 2015, 102 (03) :277-286
[2]   Recurrence Pattern After Temozolomide Concomitant With and Adjuvant to Radiotherapy in Newly Diagnosed Patients With Glioblastoma: Correlation With MGMT Promoter Methylation Status [J].
Brandes, Alba A. ;
Tosoni, Alicia ;
Franceschi, Enrico ;
Sotti, Guido ;
Frezza, Giampiero ;
Amista, Pietro ;
Morandi, Luca ;
Spagnolli, Federica ;
Ermani, Mario .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (08) :1275-1279
[3]   Seizure-susceptible brain regions in glioblastoma: identification of patients at risk [J].
Cayuela, N. ;
Simo, M. ;
Majos, C. ;
Rifa-Ros, X. ;
Gallego Perez-Larraya, J. ;
Ripolles, P. ;
Vidal, N. ;
Miro, J. ;
Gil, F. ;
Gil-Gil, M. ;
Plans, G. ;
Graus, F. ;
Bruna, J. .
EUROPEAN JOURNAL OF NEUROLOGY, 2018, 25 (02) :387-394
[4]  
Di Carlo DT, 2017, NEUROSURG REV, V42, P1, DOI DOI 10.1007/S10143-017-0928-729138949
[5]   MicroRNA-221 Targets Bmf in Hepatocellular Carcinoma and Correlates with Tumor Multifocality [J].
Gramantieri, Laura ;
Fornari, Francesca ;
Ferracin, Manuela ;
Veronese, Angelo ;
Sabbioni, Silvia ;
Calin, George Adrian ;
Grazi, Gian Luca ;
Croce, Carlo Maria ;
Bolondi, Luigi ;
Negrini, Massimo .
CLINICAL CANCER RESEARCH, 2009, 15 (16) :5073-5081
[6]   Serum microRNA profiling in patients with glioblastoma: a survival analysis [J].
Hua, Zhao ;
Shen, Jie ;
Hodges, Tiffany R. ;
Song, Renduo ;
Fuller, Gregory N. ;
Heimberger, Amy B. .
MOLECULAR CANCER, 2017, 16
[7]   MicroRNAs as biomarkers for human glioblastoma: progress and potential [J].
Huang, Shi-wei ;
Ali, Ni-da ;
Zhong, Lily ;
Shi, Jian .
ACTA PHARMACOLOGICA SINICA, 2018, 39 (09) :1405-1413
[8]   THE C-ELEGANS HETEROCHRONIC GENE LIN-4 ENCODES SMALL RNAS WITH ANTISENSE COMPLEMENTARITY TO LIN-14 [J].
LEE, RC ;
FEINBAUM, RL ;
AMBROS, V .
CELL, 1993, 75 (05) :843-854
[9]  
Liao L, 2016, CANC RES CLIN, V28, P590, DOI [10.3760/cma.j.issn.1006-9801.2016.09.004, DOI 10.3760/CMA.J.ISSN.1006-9801.2016.09.004]
[10]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408