Skip to main content
Erschienen in: Journal of Neuro-Oncology 3/2019

17.08.2019 | Clinical Study

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

verfasst von: Menha Swellam, Lobna Ezz El Arab, Amr S. Al-Posttany, Samy B. Said

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

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Blood samples were withdrawn from 20 GBM cases before and after treatment, a group of 20 healthy individuals were served as control.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.
Literatur
1.
Zurück zum Zitat Paolillo M, Boselli C, Schinelli S (2018) Glioblastoma under siege: an overview of current therapeutic strategies. Brain Sci. 8:15–20CrossRef Paolillo M, Boselli C, Schinelli S (2018) Glioblastoma under siege: an overview of current therapeutic strategies. Brain Sci. 8:15–20CrossRef
2.
Zurück zum Zitat Di Carlo DT, Cagnazzo F, Benedetto N, Morganti R, Perrini P (2017) Multiple high-grade gliomas: epidemiology, management, and outcome a systematic review and meta-analysis. Neurosurg Rev. 42:1–13 Di Carlo DT, Cagnazzo F, Benedetto N, Morganti R, Perrini P (2017) Multiple high-grade gliomas: epidemiology, management, and outcome a systematic review and meta-analysis. Neurosurg Rev. 42:1–13
3.
Zurück zum Zitat Brandes AA, Tosoni A, Franceschi E, Sotti G, Frezza G, Amistà P, Morandi L, Spagnolli F, Ermani M (2009) Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation with MGMT promoter methylation status. J Clin Oncol. 27:1275–1279CrossRef Brandes AA, Tosoni A, Franceschi E, Sotti G, Frezza G, Amistà P, Morandi L, Spagnolli F, Ermani M (2009) Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation with MGMT promoter methylation status. J Clin Oncol. 27:1275–1279CrossRef
4.
Zurück zum Zitat Lee RC, Feinbaum RL, Ambros V (1993) The C. elegansheterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854CrossRef Lee RC, Feinbaum RL, Ambros V (1993) The C. elegansheterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854CrossRef
5.
Zurück zum Zitat Visani M, de Biase D, Marucci G, Cerasoli S, Nigrisoli E, Reggiani MLB, Albani F, Baruzzi A, Pession A (2014) Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III study group. Mol Oncol. 8:417–430CrossRef Visani M, de Biase D, Marucci G, Cerasoli S, Nigrisoli E, Reggiani MLB, Albani F, Baruzzi A, Pession A (2014) Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III study group. Mol Oncol. 8:417–430CrossRef
6.
Zurück zum Zitat Sumazin P, Yang X, Chiu HS, Chung WJ, Iyer A, LIobet-Navas D, Rajbhandari P, Bansal M, Guarnieri P, Silva J, Califano A. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell. 2011. 147: 370–381.CrossRef Sumazin P, Yang X, Chiu HS, Chung WJ, Iyer A, LIobet-Navas D, Rajbhandari P, Bansal M, Guarnieri P, Silva J, Califano A. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell. 2011. 147: 370–381.CrossRef
7.
Zurück zum Zitat Riddick G, Fine HA (2011) Integration and analysis of genome-scale data from gliomas. Nat Rev Neurol 7:439–450CrossRef Riddick G, Fine HA (2011) Integration and analysis of genome-scale data from gliomas. Nat Rev Neurol 7:439–450CrossRef
8.
Zurück zum Zitat Wang B-C, Ma J (2015) Role of microRNA in malignant glioma. Chin Med J 128:1238–1244CrossRef Wang B-C, Ma J (2015) Role of microRNA in malignant glioma. Chin Med J 128:1238–1244CrossRef
9.
Zurück zum Zitat Zhao H, Shen J, Hodges TR, Song R, Fuller GN, Heimberger AB (2017) Serum microRNA profiling in patients with glioblastoma: a survival analysis. Mol Cancer. 16:59–66CrossRef Zhao H, Shen J, Hodges TR, Song R, Fuller GN, Heimberger AB (2017) Serum microRNA profiling in patients with glioblastoma: a survival analysis. Mol Cancer. 16:59–66CrossRef
10.
Zurück zum Zitat Gramantieri L, Fornari F, Ferracin M, Veronese A, Sabbioni S, Calin GA, Grazi GL, Croce CM, Bolondi L, Negrini M (2009) MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality. Clin Cancer Res. 15(16):5073–5081CrossRef Gramantieri L, Fornari F, Ferracin M, Veronese A, Sabbioni S, Calin GA, Grazi GL, Croce CM, Bolondi L, Negrini M (2009) MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality. Clin Cancer Res. 15(16):5073–5081CrossRef
11.
Zurück zum Zitat Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, Miller K, Lein M, Kristiansen G, Jung K (2010) Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 126(5):1166–1176PubMed Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, Miller K, Lein M, Kristiansen G, Jung K (2010) Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 126(5):1166–1176PubMed
12.
Zurück zum Zitat Liao L, Wang J, Feng S, Lan Z (2016) The expression of MIR-221 and MIR-222 in non-small cell lung cancer and their significances. Cancer Res Clin. 28:590–594 Liao L, Wang J, Feng S, Lan Z (2016) The expression of MIR-221 and MIR-222 in non-small cell lung cancer and their significances. Cancer Res Clin. 28:590–594
13.
Zurück zum Zitat Swellam M, ElMagdoub HM, Hassan NM, Hefny MM, Sobeih ME (2018) Potential diagnostic role of circulating MiRNAs in breast cancer implications on clinicopathological characters. Clin Biochem. 56:47–54CrossRef Swellam M, ElMagdoub HM, Hassan NM, Hefny MM, Sobeih ME (2018) Potential diagnostic role of circulating MiRNAs in breast cancer implications on clinicopathological characters. Clin Biochem. 56:47–54CrossRef
15.
Zurück zum Zitat Zhang C, Zhang J, Hao J, Shi Z, Wang Y, Han L, You Y, Jiang T, Wang J, Liu M, Pu P, Kang C (2012) High level of miR-221/222 confers increased cell invasion and poor prognosis in glioma. J Trans Med. 10:119–130CrossRef Zhang C, Zhang J, Hao J, Shi Z, Wang Y, Han L, You Y, Jiang T, Wang J, Liu M, Pu P, Kang C (2012) High level of miR-221/222 confers increased cell invasion and poor prognosis in glioma. J Trans Med. 10:119–130CrossRef
16.
Zurück zum Zitat Toraih EA, Aly NM, Abdallah HY, Al-Qahtani SA, Shaalan AA, Hussein MH, Fawzy MS (2017) MicroRNA–target cross-talks: key playersin glioblastoma multiforme. Tumour Biol. 39:1–22CrossRef Toraih EA, Aly NM, Abdallah HY, Al-Qahtani SA, Shaalan AA, Hussein MH, Fawzy MS (2017) MicroRNA–target cross-talks: key playersin glioblastoma multiforme. Tumour Biol. 39:1–22CrossRef
17.
Zurück zum Zitat Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol. 5:649–655CrossRef Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol. 5:649–655CrossRef
18.
Zurück zum Zitat Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta DeltaC(T)) method. Methods 25(4):402–408CrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta DeltaC(T)) method. Methods 25(4):402–408CrossRef
19.
Zurück zum Zitat Zweig MH, Campbell G (1993) Receiver operating characteristics (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 39:561–577PubMed Zweig MH, Campbell G (1993) Receiver operating characteristics (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 39:561–577PubMed
20.
Zurück zum Zitat Huang SW, Ali ND, Zhong L, Shi J (2018) MicroRNAs as biomarkers for human glioblastoma: progress and potential. Acta Pharmacol Sinica 39:1405–1413CrossRef Huang SW, Ali ND, Zhong L, Shi J (2018) MicroRNAs as biomarkers for human glioblastoma: progress and potential. Acta Pharmacol Sinica 39:1405–1413CrossRef
21.
Zurück zum Zitat Zhou X, Ren Y, Moore L, Mei M, You Y, Xu P, Wang B, Wang G, Jia Z, Pu P, Zhang W, Kang C (2010) Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Lab Investig. 90:144–155CrossRef Zhou X, Ren Y, Moore L, Mei M, You Y, Xu P, Wang B, Wang G, Jia Z, Pu P, Zhang W, Kang C (2010) Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Lab Investig. 90:144–155CrossRef
22.
Zurück zum Zitat Biau J, Dalloz P, Durando X, Hager MO, Ouédraogo ZG, Khalil T, Lemaire JJ, Chautard E, Varrelle P (2015) Elderly patients with glioblastoma: state of the art. Cancer Bull. 102(3):277–286CrossRef Biau J, Dalloz P, Durando X, Hager MO, Ouédraogo ZG, Khalil T, Lemaire JJ, Chautard E, Varrelle P (2015) Elderly patients with glioblastoma: state of the art. Cancer Bull. 102(3):277–286CrossRef
23.
Zurück zum Zitat Smrdel U, Vidmar MS, Smrdel A (2018) Glioblastoma in patients over 70 years of age. Radiol Oncol. 52(2):167–172CrossRef Smrdel U, Vidmar MS, Smrdel A (2018) Glioblastoma in patients over 70 years of age. Radiol Oncol. 52(2):167–172CrossRef
25.
Zurück zum Zitat Cayuelaa N, Simo M, Majos C, Rifa-Ros X, Gallego J, Erez-Larraya P, Ripolles P, Vidala N, Miro J, Gild F, Gil-Gila M, Plansa G, Grausd F, Brunaa J (2017) Seizure-susceptible brain regions in glioblastoma: identification of patients at risk. Eur J Neurol. https://doi.org/10.1111/ene.13518 CrossRef Cayuelaa N, Simo M, Majos C, Rifa-Ros X, Gallego J, Erez-Larraya P, Ripolles P, Vidala N, Miro J, Gild F, Gil-Gila M, Plansa G, Grausd F, Brunaa J (2017) Seizure-susceptible brain regions in glioblastoma: identification of patients at risk. Eur J Neurol. https://​doi.​org/​10.​1111/​ene.​13518 CrossRef
26.
Zurück zum Zitat Zhu P, Du X, Lu G, Zhu JJ (2017) Survival benefit of glioblastoma patients after FDA approval of temozolomide concomitant with radiation and bevacizumab a population-based study. Oncotarget. 8(27):44015–44031CrossRef Zhu P, Du X, Lu G, Zhu JJ (2017) Survival benefit of glioblastoma patients after FDA approval of temozolomide concomitant with radiation and bevacizumab a population-based study. Oncotarget. 8(27):44015–44031CrossRef
Metadaten
Titel
Clinical impact of circulating oncogenic MiRNA-221 and MiRNA-222 in glioblastoma multiform
verfasst von
Menha Swellam
Lobna Ezz El Arab
Amr S. Al-Posttany
Samy B. Said
Publikationsdatum
17.08.2019
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 3/2019
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-019-03256-2

Weitere Artikel der Ausgabe 3/2019

Journal of Neuro-Oncology 3/2019 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.