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Dynamic expression of 11 miRNAs in 83 consecutive primary and corresponding recurrent glioblastoma: correlation to treatment, time to recurrence, overall survival and MGMT methylation status

Bostjan Matos
Bostjan Matos
, 
Emanuela Bostjancic
Emanuela Bostjancic
, 
Alenka Matjasic
Alenka Matjasic
, 
Mara Popovic
Mara Popovic
 oraz 
Damjan Glavac
Damjan Glavac
   | 26 lis 2018
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Article Category: Research Article
Data publikacji: 26 lis 2018
Zakres stron: 422 - 432
Otrzymano: 06 sie 2018
Przyjęty: 03 wrz 2018
DOI: https://doi.org/10.2478/raon-2018-0043
© 2018 Bostjan Matos, Emanuela Bostjancic, Alenka Matjasic, Mara Popovic, Damjan Glavac, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

FIGURE 1

Schematic representation of the workflow and statistical comparisons.GBM = glioblastoma; Reference RNA = Human Brain Reference RNA; 1 = Willcoxon Signed Rank Test between primary glioblastoma and corresponding recurrent glioblastoma using ΔCt; 2 = normalization to Human Brain reference RNA resulting in ΔΔCt; 3 and 4 = Mann-Whitney test between independent groups of samples using ΔΔCt (normalization of glioblastoma samples to Human Brain Reference RNA)
Schematic representation of the workflow and statistical comparisons.GBM = glioblastoma; Reference RNA = Human Brain Reference RNA; 1 = Willcoxon Signed Rank Test between primary glioblastoma and corresponding recurrent glioblastoma using ΔCt; 2 = normalization to Human Brain reference RNA resulting in ΔΔCt; 3 and 4 = Mann-Whitney test between independent groups of samples using ΔΔCt (normalization of glioblastoma samples to Human Brain Reference RNA)

FIGURE 2

Expression of miRNAs in primary and recurrent GBM (compared to the Human Brain Reference RNA, ΔΔCt) with Table presenting Average Fold Changes.ChT = chemotherapy; RT = radiotherapy; A = primary GBM; B = recurrent GBM
Expression of miRNAs in primary and recurrent GBM (compared to the Human Brain Reference RNA, ΔΔCt) with Table presenting Average Fold Changes.ChT = chemotherapy; RT = radiotherapy; A = primary GBM; B = recurrent GBM

FIGURE 3

Expression of miRNAs in recurrent glioblastoma (GBM) after treatment compared to expression in primary GBM. Results are represented separately for patients treated with RT and those treated with RT and ChT.ChT = chemotherapy; RT = radiotherapy; * = significant differences in expression of miRNAs, p < 0.05; ** = p < 0.01
Expression of miRNAs in recurrent glioblastoma (GBM) after treatment compared to expression in primary GBM. Results are represented separately for patients treated with RT and those treated with RT and ChT.ChT = chemotherapy; RT = radiotherapy; * = significant differences in expression of miRNAs, p < 0.05; ** = p < 0.01

FIGURE 4

Distinctive expression of miRNAs after different treatment options in recurrent glioblastomaChT = chemotherapy; RT = radiotherapy; * = p < 0.05; ** = p < 0.01
Distinctive expression of miRNAs after different treatment options in recurrent glioblastomaChT = chemotherapy; RT = radiotherapy; * = p < 0.05; ** = p < 0.01

FIGURE 5

Survival curve analyses; (A) Progression free survival between patients that received RT alone or both, RT and ChT; (B) Survival time after second surgery for patients who received no therapy versus patients who received ChT; (C) Progression free survival between patients with up- and downregulated miR-26b; (D) Progression free survival between patients with up- and downregulated let-7f.ChT = chemotherapy; RT = radiotherapy
Survival curve analyses; (A) Progression free survival between patients that received RT alone or both, RT and ChT; (B) Survival time after second surgery for patients who received no therapy versus patients who received ChT; (C) Progression free survival between patients with up- and downregulated miR-26b; (D) Progression free survival between patients with up- and downregulated let-7f.ChT = chemotherapy; RT = radiotherapy

FIGURE 6

Summary of known functions in radio- and chemoresistance and sensitivity of miRNAs analyzed in our study.
Summary of known functions in radio- and chemoresistance and sensitivity of miRNAs analyzed in our study.

List of the analysed miRNAs with known functions in glioma pathogenesis

MicroRNAsInvasionProliferationTu growthMigrationCell cyclecell Survival/deathOther functions
miR-7+++nd++Differentiation, Vasculogenic mimicry
miR-9nd+nd+ndndSelf-renewal, Vasculogenic mimicry
miR-15b+++nd++Angiogenesis
miR-21++++++/
miR-26b++++nd+Vasculogenic mimicry
miR-124++++++Differentiation, Angiogenesis
miR-199and+ndndndnd/
let-7and+++ndnd/
let-7b+ndnd+ndnd/
let-7dndndndndndnd/
let-7f++nd+ndnd/

Demographic and clinicopathological characteristics of patients included in the study

Histopathological diagnosisGBM, grade WHO IV
Number of cases83
Mean age (Year)50 (min ± 12.8 8, max 71)
Male50 (60%)
Gender
Female33 (40%)
Karnofsky performance status ≥ 8083
radiotherapy after first surgery83/83 (100%)
chemotherapy after first surgery54/83 (65%)
Adjuvant treatment
radiotherapy after second surgery15/83 (18%)
chemotherapy after second surgery47/83 (56%)
MGMT (tested methylated in a subset of patients treated with TMZ)Primary GBM38/47 (81%)
Recurrent GBM46/47 (98%)
Time to recurrence (months)0.84–67.30
Survival after second surgery (months)0.03–25.75
Overall survival (months)0.84–70.48
eISSN:
1581-3207
Język:
Angielski
Częstotliwość wydawania:
4 razy w roku
Dziedziny czasopisma:
Medicine, Clinical Medicine, Radiology, Internal Medicine, Haematology, Oncology
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