Abstract
Serum miRNAs (miRs) have gained consideration as encouraging molecular markers for cancer diagnosis and prediction of prognosis. The authors aimed to identify the exact role of miR-17-5p, miR-125b, and miR-221 among glioblastoma multiforme (GBM) patients before and after standard treatment, and correlate their expression with survival pattern. The study included 25 GBM patients and 20 healthy controls. Serum miR-17-5p, miR-125b, and miR-221 expression were analyzed before and after treatment using quantitative real-time polymerase chain reaction (qPCR). The diagnostic efficacy for the tested miRs was evaluated using the receiver operating characteristic (ROC) curve, and the relation of miRs expression versus clinical criteria for GBM was assessed. Patients’ survival patterns were examined versus miRs expression levels. A significant difference was reported between miRs expression among the enrolled individuals. Both miR-17-5p and miR-221 reported significant elevations in GBM patients who: are above 60 years old, underwent biopsy resection, have a non-frontal lesion, with tumor size above 5 cm, and with performance status equals 2 according to the Eastern Cooperative Oncology Group (ECOG) Performance Status. With regard to miR-125b, a significant difference was detected according to surgery strategy, primary lesion of the tumor, and ECOG status. MiRs levels were significantly decreased for GBM patients after treatment. Survival patterns demonstrated an increase in miR-17-5p, miR-125b, and miR-221 in GBM patients with worse progression-free survival and among those with worse overall survival. Detection of serum miR-17-5p, miR-125b, and miR-221 aids in the prediction of prognosis and response to treatment strategy for GBM patients.
Similar content being viewed by others
References
Bobbili MR, Mader RM, Grillari J, Dellago H (2017) OncomiR-17-5p: alarm signal in cancer? Oncotarget 8(41):71206–71222
Chaudhary V, Jangra S, Yadav NR (2018) Nanotechnology-based approaches for detection and delivery of microRNA in healthcare and crop protection. J Nanobiotechnology 16(1):40
Chen Q, Si Q, Xiao S, Xie Q, Lin J, Wang C, Chen L, Wang L (2013) Prognostic significance of serum miR-17-5p in lung cancer. Med Oncol 30(1):353
Coller HA, Forman JJ, Legesse-Miller A (2007) "Myc'ed messages": myc induces transcription of E2F1 while inhibiting its translation via a microRNA polycistron. PLoS Genet 3(8):e146
Crespo I, Vital AL, Gonzalez-Tablas M, Patino Mdel C, Otero A, Lopes MC, de Oliveira C, Domingues P, Orfao A, Tabernero MD (2015) Molecular and genomic alterations in glioblastoma multiforme. Am J Pathol 185(7):1820–1833
Dahlrot RH, Hermansen SK, Hansen S, Kristensen BW (2013) What is the clinical value of cancer stem cell markers in gliomas? Int J Clin Exp Pathol 6(3):334–348
Delangle R, De Foucher T, Larsen AK, Sabbah M, Azais H, Bendifallah S, Darai E, Ballester M, Mehats C, Uzan C, Canlorbe G (2019) The use of microRNAs in the management of endometrial cancer: a meta-analysis. Cancers 11(6):832
Dong L, Li Y, Han C, Wang X, She L, Zhang H (2014) miRNA microarray reveals specific expression in the peripheral blood of glioblastoma patients. Int J Oncol 45(2):746–756
Ernst A, Campos B, Meier J, Devens F, Liesenberg F, Wolter M, Reifenberger G, Herold-Mende C, Lichter P, Radlwimmer B (2010) De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures. Oncogene 29(23):3411–3422
Haemmig S, Baumgartner U, Gluck A, Zbinden S, Tschan MP, Kappeler A, Mariani L, Vajtai I, Vassella E (2014) miR-125b controls apoptosis and temozolomide resistance by targeting TNFAIP3 and NKIRAS2 in glioblastomas. Cell Death Dis 5:e1279
Hench IB, Hench J, Tolnay M (2018) Liquid biopsy in clinical management of breast, lung, and colorectal cancer. Front Med 5:9–9
Jiang Y, Luan Y, Chang H, Chen G (2018) The diagnostic and prognostic value of plasma microRNA-125b-5p in patients with multiple myeloma. Oncol Lett 16(3):4001–4007
Kiener M, Chen L, Krebs M, Grosjean J, Klima I, Kalogirou C, Riedmiller H, Kneitz B, Thalmann GN, Snaar-Jagalska E, Spahn M, Kruithof-de Julio M, Zoni E (2019) miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo. BMC Cancer 19(1): 627
Kong W, Cheng Y, Liang H, Chen Q, Xiao C, Li K, Huang Z, Zhang J (2018) Prognostic value of miR-17-5p in cancers: a meta-analysis. Onco Targets Ther 11:3541–3549
Lee J, Park SH, Kim YZ (2018) Prognostic evaluation of neurological assessment of the neuro-oncology scale in glioblastoma patients. Brain Tumor Res Treat 6(1):22–30
Li S, Zeng A, Hu Q, Yan W, Liu Y, You Y (2017) miR-423-5p contributes to a malignant phenotype and temozolomide chemoresistance in glioblastomas. Neuro-Oncol 19(1):55–65
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25(4):402–408
Mabray MC, Barajas RF Jr, Cha S (2015) Modern brain tumor imaging. Brain Tumor Res Treat 3(1):8–23
Mitchell P, Ellison DW, Mendelow AD (2005) Surgery for malignant gliomas: mechanistic reasoning and slippery statistics. Lancet Neurol 4(7):413–422
Mooney C, Raoof R, El-Naggar H, Sanz-Rodriguez A, Jimenez-Mateos EM, Henshall DC (2015) High throughput qPCR expression profiling of circulating MicroRNAs reveals minimal sex- and sample timing-related variation in plasma of healthy volunteers. PLoS One 10(12):e0145316
Morales LD, Casillas Pavon EA, Shin JW, Garcia A, Capetillo M, Kim DJ, Lieman JH (2014) Protein tyrosine phosphatases PTP-1B, SHP-2, and PTEN facilitate Rb/E2F-associated apoptotic signaling. PLoS One 9(5):e97104
Paldor I, Pearce FC, Drummond KJ, Kaye AH (2016) Frontal glioblastoma multiforme may be biologically distinct from non-frontal and multilobar tumors. J Clin Neurosci 34:128–132
Pichler M, Calin GA (2015) MicroRNAs in cancer: from developmental genes in worms to their clinical application in patients. Br J Cancer 113(4):569–573
Quintavalle C, Mangani D, Roscigno G, Romano G, Diaz-Lagares A, Iaboni M, Donnarumma E, Fiore D, De Marinis P, Soini Y, Esteller M, Condorelli G (2013) MiR-221/222 target the DNA methyltransferase MGMT in glioma cells. PLoS One 8(9):e74466
Rolle K (2015) miRNA multiplayers in glioma. From bench to bedside. Acta Biochim Pol 62(3):353–365
Sasaki K, Kohanbash G, Hoji A, Ueda R, McDonald HA, Reinhart TA, Martinson J, Lotze MT, Marincola FM, Wang E, Fujita M, Okada H (2010) miR-17-92 expression in differentiated T cells - implications for cancer immunotherapy. J Transl Med 8:17
Shea A, Harish V, Afzal Z, Chijioke J, Kedir H, Dusmatova S, Roy A, Ramalinga M, Harris B, Blancato J, Verma M, Kumar D (2016) MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics. Cancer Med 5(8):1917–1946
Shiroishi MS, Boxerman JL, Pope WB (2016) Physiologic MRI for assessment of response to therapy and prognosis in glioblastoma. Neuro-Oncol 18(4):467–478
Sohel MH (2016) Extracellular/circulating MicroRNAs: release mechanisms, functions and challenges. Achiev Life Sci 10(2):175–186
Song J, Ouyang Y, Che J, Li X, Zhao Y, Yang K, Zhao X, Chen Y, Fan C, Yuan W (2017) Potential value of miR-221/222 as diagnostic, prognostic, and therapeutic biomarkers for diseases. Front Immunol 8:56
Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10(5):459–466
Sun YM, Lin KY, Chen YQ (2013) Diverse functions of miR-125 family in different cell contexts. J Hematol Oncol 6:6
Swellam M, Ramadan A (2019). Clinical significance of blood-based miRNAs as diagnostic and prognostic nucleic acid markers in breast cancer: comparative to conventional tumor markers. J Cell Biochem 120(8): 12321–12330
Swellam M, El Magdoub HM, Hassan NM, Hefny MM, Sobeih ME (2018a) Potential diagnostic role of circulating MiRNAs in breast cancer: implications on clinicopathological characters. Clin Biochem 56:47–54
Swellam M, Hashim M, Mahmoud MS, Ramadan A, Hassan NM (2018b) Aberrant expression of some circulating miRNAs in childhood acute lymphoblastic leukemia. Biochem Genet 56(4):283–294
Swellam M, Ezz El Arab L, Al-Posttany AS, Said SB (2019) Clinical impact of circulating oncogenic MiRNA-221 and MiRNA-222 in glioblastoma multiform. J Neuro-Oncol 144(3):545–551
Tili E, Michaille JJ, Croce CM (2013) MicroRNAs play a central role in molecular dysfunctions linking inflammation with cancer. Immunol Rev 253(1):167–184
Vartanian A, Singh SK, Agnihotri S, Jalali S, Burrell K, Aldape KD, Zadeh G (2014) GBM's multifaceted landscape: highlighting regional and microenvironmental heterogeneity. Neuro-Oncol 16(9):1167–1175
Xie Q, Yan Y, Huang Z, Zhong X, Huang L (2014) MicroRNA-221 targeting PI3-K/Akt signaling axis induces cell proliferation and BCNU resistance in human glioblastoma. Neuropathology 34(5):455–464
Yuan GQ, Wei NL, Mu LY, Wang XQ, Zhang YN, Zhou WN, Pan YW (2017) A 4-miRNAs signature predicts survival in glioblastoma multiforme patients. Cancer Biomark 20:443–452
Zeng AL, Yan W, Liu YW, Wang Z, Hu Q, Nie E, Zhou X, Li R, Wang XF, Jiang T, You YP (2017) Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant phenotype and temozolomide chemoresistance in glioblastoma. Oncogene 36(38):5369–5381
Zeng A, Yin J, Li Y, Li R, Wang Z, Zhou X, Jin X, Shen F, Yan W, You Y (2018a) miR-129-5p targets Wnt5a to block PKC/ERK/NF-kappaB and JNK pathways in glioblastoma. Cell Death Dis 9(3):394
Zeng A, Yin J, Wang Z, Zhang C, Li R, Zhang Z, Yan W, You Y (2018b) miR-17-5p-CXCL14 axis related transcriptome profile and clinical outcome in diffuse gliomas. Oncoimmunology 7(12):e1510277
Zhang C, Cheng W, Ren X, Wang Z, Liu X, Li G, Han S, Jiang T, Wu A (2017) Tumor purity as an underlying key factor in glioma. Clin Cancer Res 23(20):6279–6291
Zhang Y, Li M, Gao X, Chen Y, Liu T (2019) Nanotechnology in cancer diagnosis: progress, challenges and opportunities. J Hematol Oncol 12(1):137
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(1):59–59
Zweig PL, Campbell RA (2014) Response to "drug shortages and the burden of access to care: a critical issue affecting patients with cancer". Clin J Oncol Nurs 18(2):143–145
Acknowledgments
The instruments listed in the current study were purchased through a grant from Science and Technology Development Fund (STDF) through Capacity Building Grant Fund (CBG) [No. 4940].
Author information
Authors and Affiliations
Contributions
Study conception and design: MS; NMB; HME; MSH and LRE. Provision of samples and clinical follow-up: LRE. Acquisition of data: NMB; HME; MSH and LRE. Analysis and interpretation of data: MS; NMB; HME and MSH. Drafting of manuscript: MS; NMB; HME and MSH. Critical revision: MS; NMB; HME; MSH and LRE.
Corresponding author
Ethics declarations
Conflict of interests
Authors confirmed that there is nothing to declare.
Ethical approval and consent to participate
were obtained from Medical Ethical Committee from National Research Centre (ID 17111), and all individuals signed their written informed consent.
Consent for publication
Authors agreed to publish work after finalizing the manuscript.
Availability of supporting data
No availability of sharing of data.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Swellam, M., Bakr, N.M., El Magdoub, H.M. et al. Emerging role of miRNAs as liquid biopsy markers for prediction of glioblastoma multiforme prognosis. J Mol Neurosci 71, 836–844 (2021). https://doi.org/10.1007/s12031-020-01706-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-020-01706-5