Comparison of microRNA expression levels between initial and recurrent glioblastoma specimens
- 675 Downloads
Glioblastoma is the most frequent primary brain tumour in adults. Recent therapeutic advances increased patient's survival, but tumour recurrence inevitably occurs. The pathobiological mechanisms involved in glioblastoma recurrence are still unclear. MicroRNAs are small RNAs proposed o have important roles for cancer including proliferation, aggressiveness and metastases development. There exist only few data on the involvement of microRNAs in glioblastoma recurrence. We selected the following 7 microRNAs with potential relevance for glioblastoma pathobiology by means of a comprehensive literature search: microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195, microRNA-221 and microRNA-222. We further selected 15 primary glioblastoma patients, of whom formalin fixed and paraffin embedded tissue (FFPE) of the initial and recurrence surgery were available. All patients had received first line treatment consisting of postoperative combined radiochemotherapy with temozolomide (n = 15). Non-neoplastic brain tissue samples from 3 patients with temporal lobe epilepsy served as control. The expression of the microRNAs were analysed by RT-qPCR. These were correlated with each other and with clinical parameters. All microRNAs showed detectable levels of expressions in glioblastoma group, whereas microRNA-10b was not detectable in epilepsy patients. MicroRNAs except microRNA-21 showed significantly higher levels in epilepsy patients when compared to the levels of first resection of glioblastoma. Comparison of microRNA levels between first and second resections revealed no significant change. Cox regression analyses showed no significant association of microRNA expression levels in the tumor tissue with progression free survival times. Expression levels of microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195, microRNA-221 and microRNA-222 do not differ significantly between initial and recurrent glioblastoma.
KeywordsGlioblastoma Recurrence MicroRNA FFPE tissue
We thank Ms. Zeljka Stajanovic for the technical assistance. This work was financed with a grant from “Hochschuljubiläumsstiftung der Stadt Wien” with the grant number H-2234/2011. This project received a Poster Award at the European Association of Neuro-oncology (EANO X) Meeting in September 2012 Marseille, France.
Conflict of interest
None of the authors declares a conflict of interest with regard to the manuscript contents.
- 1.Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRefGoogle Scholar
- 9.Slaby O, Lakomy R, Fadrus P, Hrstka R, Kren L, Lzicarova E, Smrcka M, Svoboda M, Dolezalova H, Novakova J, Valik D, Vyzula R, Michalek J (2010) MicroRNA-181 family predicts response to concomitant chemoradiotherapy with temozolomide in glioblastoma patients. Neoplasma 57:264–269PubMedCrossRefGoogle Scholar
- 12.Preusser M, Hoeftberger R, Woehrer A, Gelpi E, Kouwenhoven M, Kros JM, Sanson M, Idbaih A, Brandes AA, Heinzl H, Gorlia T, Hainfellner JA, van den Bent M (2012) Prognostic value of Ki67 index in anaplastic oligodendroglial tumours–a translational study of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Histopathology 60:885–894PubMedCrossRefGoogle Scholar
- 14.Quintavalle C, Garofalo M, Zanca C, Romano G, Iaboni M, del Basso De Caro M, Martinez-Montero JC, Incoronato M, Nuovo G, Croce CM, Condorelli G (2012) MiR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPmu. Oncogene 31: 858–868Google Scholar
- 16.Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, Vandenberg SR, Ginzinger DG, James CD, Costello JF, Bergers G, Weiss WA, Alvarez-Buylla A, Hodgson JG (2008) MiR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC medicine 6:14PubMedCrossRefGoogle Scholar
- 18.Lakomy R, Sana J, Hankeova S, Fadrus P, Kren L, Lzicarova E, Svoboda M, Dolezelova H, Smrcka M, Vyzula R, Michalek J, Hajduch M, Slaby O (2011) MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients. Cancer Sci 102:2186–2190PubMedCrossRefGoogle Scholar
- 29.Quintavalle C, Donnarumma E, Iaboni M, Roscigno G, Garofalo M, Romano G, Fiore D, De Marinis P, Croce CM, Condorelli G (2012) Effect of miR-21 and miR-30b/c on TRAIL-induced apoptosis in glioma cells. Oncogene. doi: 10.1038/onc.2012.410