Adverse prognosis of glioblastoma contacting the subventricular zone: Biological correlates

English version

Autoři: Sharon Berendsen ^aff001; Emma van Bodegraven ^aff002; Tatjana Seute ^aff001; Wim G. M. Spliet ^aff003; Marjolein Geurts ^aff001; Jeroen Hendrikse ^aff004; Laurent Schoysman ^aff005; Willemijn B. Huiszoon ^aff001; Meri Varkila ^aff001; Soufyan Rouss ^aff001; Erica H. Bell ^aff007; Jérôme Kroonen ^aff001; Arnab Chakravarti ^aff007; Vincent Bours ^aff005; Tom J. Snijders ^aff001; Pierre A. Robe ^aff001
Působiště autorů: UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of Utrecht, Utrecht, The Netherlands ^aff001; UMC Utrecht Brain Center, Department of Translational Neuroscience, University Medical Center of Utrecht, Utrecht, The Netherlands ^aff002; Department of Pathology, University Medical Center of Utrecht, Utrecht, The Netherlands ^aff003; Department of Radiology, University Medical Center of Utrecht, Utrecht, The Netherlands ^aff004; Department of Human Genetics, GIGA Research Center, Liège University Hospital, Liège, Belgium ^aff005; Department of Radiology, Liège University Hospital, Liège, Belgium ^aff006; Department of Radiation Oncology, Wexner Medical Center, James Cancer Center, Ohio State University, Columbus, OH, United States of America ^aff007
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0222717

Souhrn

Introduction

The subventricular zone (SVZ) in the brain is associated with gliomagenesis and resistance to treatment in glioblastoma. In this study, we investigate the prognostic role and biological characteristics of subventricular zone (SVZ) involvement in glioblastoma.

Methods

We analyzed T1-weighted, gadolinium-enhanced MR images of a retrospective cohort of 647 primary glioblastoma patients diagnosed between 2005–2013, and performed a multivariable Cox regression analysis to adjust the prognostic effect of SVZ involvement for clinical patient- and tumor-related factors. Protein expression patterns of a.o. markers of neural stem cellness (CD133 and GFAP-δ) and (epithelial-) mesenchymal transition (NF-κB, C/EBP-β and STAT3) were determined with immunohistochemistry on tissue microarrays containing 220 of the tumors. Molecular classification and mRNA expression-based gene set enrichment analyses, miRNA expression and SNP copy number analyses were performed on fresh frozen tissue obtained from 76 tumors. Confirmatory analyses were performed on glioblastoma TCGA/TCIA data.

Results

Involvement of the SVZ was a significant adverse prognostic factor in glioblastoma, independent of age, KPS, surgery type and postoperative treatment. Tumor volume and postoperative complications did not explain this prognostic effect. SVZ contact was associated with increased nuclear expression of the (epithelial-) mesenchymal transition markers C/EBP-β and phospho-STAT3. SVZ contact was not associated with molecular subtype, distinct gene expression patterns, or markers of stem cellness. Our main findings were confirmed in a cohort of 229 TCGA/TCIA glioblastomas.

Conclusion

In conclusion, involvement of the SVZ is an independent prognostic factor in glioblastoma, and associates with increased expression of key markers of (epithelial-) mesenchymal transformation, but does not correlate with stem cellness, molecular subtype, or specific (mi)RNA expression patterns.

Klíčová slova:

Gene expression – Cancer treatment – MicroRNAs – Magnetic resonance imaging – Surgical and invasive medical procedures – Surgical oncology – Prognosis – Glioblastoma multiforme

Zdroje

1. Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, et al. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015;314(23):2535–43. doi: 10.1001/jama.2015.16669 26670971

2. Ellingson BM, Cloughesy TF, Pope WB, Zaw TM, Phillips H, Lalezari S, et al. Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas. NeuroImage. 2012;59(2):908–16. doi: 10.1016/j.neuroimage.2011.09.076 22001163

3. Smith TR, Hulou MM, Abecassis J, Das S, Chandler JP. Use of preoperative FLAIR MRI and ependymal proximity of tumor enhancement as surrogate markers of brain tumor origin. Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia. 2015;22(9):1397–402. doi: 10.1016/j.jocn.2015.02.029 26055954

4. Sanai N, Alvarez-Buylla A, Berger MS. Neural stem cells and the origin of gliomas. The New England Journal of Medicine. 2005;353(8):811–22. doi: 10.1056/NEJMra043666 16120861

5. Wang Y, Yang J, Zheng H, Tomasek GJ, Zhang P, McKeever PE, et al. Expression of mutant p53 proteins implicates a lineage relationship between neural stem cells and malignant astrocytic glioma in a murine model. Cancer Cell. 2009;15(6):514–26. doi: 10.1016/j.ccr.2009.04.001 19477430

6. Lee JH, Lee JE, Kahng JY, Kim SH, Park JS, Yoon SJ, et al. Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature. 2018;560(7717):243–7. Epub 2018/08/03. doi: 10.1038/s41586-018-0389-3 30069053.

7. Kroonen J, Nassen J, Boulanger YG, Provenzano F, Capraro V, Bours V, et al. Human glioblastoma-initiating cells invade specifically the subventricular zones and olfactory bulbs of mice after striatal injection. International Journal of Cancer. 2011;129(3):574–85. doi: 10.1002/ijc.25709 20886597

8. Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB, et al. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Research. 2006;66(16):7843–8. doi: 10.1158/0008-5472.CAN-06-1010 16912155

9. Lee P, Eppinga W, Lagerwaard F, Cloughesy T, Slotman B, Nghiemphu PL, et al. Evaluation of high ipsilateral subventricular zone radiation therapy dose in glioblastoma: a pooled analysis. Int J Radiat Oncol Biol Phys. 2013;86(4):609–15. Epub 2013/03/07. doi: 10.1016/j.ijrobp.2013.01.009 23462418.

10. Goffart N, Kroonen J, Di Valentin E, Dedobbeleer M, Denne A, Martinive P, et al. Adult mouse subventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR4 signaling. Neuro-Oncology. 2015;17(1):81–94. doi: 10.1093/neuonc/nou144 25085362

11. Goffart N, Lombard A, Lallemand F, Kroonen J, Nassen J, Di Valentin E, et al. CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone. Neuro-Oncology. 2017;19(1):66–77. Epub 2016/07/03. doi: 10.1093/neuonc/now136 27370398; PubMed Central PMCID: PMC5193023.

12. Chen L, Chaichana KL, Kleinberg L, Ye X, Quinones-Hinojosa A, Redmond K. Glioblastoma recurrence patterns near neural stem cell regions. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology. 2015;116(2):294–300. doi: 10.1016/j.radonc.2015.07.032 26276527

13. Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012;488(7412):522–6. doi: 10.1038/nature11287 22854781

14. Adeberg S, Konig L, Bostel T, Harrabi S, Welzel T, Debus J, et al. Glioblastoma recurrence patterns after radiation therapy with regard to the subventricular zone. Int J Radiat Oncol Biol Phys. 2014;90(4):886–93. Epub 2014/09/16. doi: 10.1016/j.ijrobp.2014.07.027 25220720.

15. Lim DA, Cha S, Mayo MC, Chen MH, Keles E, VandenBerg S, et al. Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro-Oncology. 2007;9(4):424–9. doi: 10.1215/15228517-2007-023 17622647

16. Kappadakunnel M, Eskin A, Dong J, Nelson SF, Mischel PS, Liau LM, et al. Stem cell associated gene expression in glioblastoma multiforme: relationship to survival and the subventricular zone. Journal of Neuro-Oncology. 2010;96(3):359–67. Epub 2009/08/06. doi: 10.1007/s11060-009-9983-4 19655089; PubMed Central PMCID: PMC2808508.

17. Chaichana KL, McGirt MJ, Frazier J, Attenello F, Guerrero-Cazares H, Quinones-Hinojosa A. Relationship of glioblastoma multiforme to the lateral ventricles predicts survival following tumor resection. Journal of Neuro-Oncology. 2008;89(2):219–24. Epub 2008/05/07. doi: 10.1007/s11060-008-9609-2 18458819.

18. Jungk C, Warta R, Mock A, Friauf S, Hug B, Capper D, et al. Location-Dependent Patient Outcome and Recurrence Patterns in IDH1-Wildtype Glioblastoma. Cancers. 2019;11(1). Epub 2019/01/24. doi: 10.3390/cancers11010122 30669568; PubMed Central PMCID: PMC6356480.

19. Gevaert O, Mitchell LA, Achrol AS, Xu J, Echegaray S, Steinberg GK, et al. Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features. Radiology. 2014;273(1):168–74. doi: 10.1148/radiol.14131731 24827998

20. Diehn M, Nardini C, Wang DS, McGovern S, Jayaraman M, Liang Y, et al. Identification of noninvasive imaging surrogates for brain tumor gene-expression modules. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(13):5213–8. doi: 10.1073/pnas.0801279105 18362333

21. Gutman DA, Cooper LA, Hwang SN, Holder CA, Gao J, Aurora TD, et al. MR imaging predictors of molecular profile and survival: multi-institutional study of the TCGA glioblastoma data set. Radiology. 2013;267(2):560–9. doi: 10.1148/radiol.13120118 23392431

22. Jungk C, Mock A, Exner J, Geisenberger C, Warta R, Capper D, et al. Spatial transcriptome analysis reveals Notch pathway-associated prognostic markers in IDH1 wild-type glioblastoma involving the subventricular zone. BMC Med. 2016;14(1):170. Epub 2016/10/27. doi: 10.1186/s12916-016-0710-7 27782828; PubMed Central PMCID: PMC5080721.

23. Itakura H, Achrol AS, Mitchell LA, Loya JJ, Liu T, Westbroek EM, et al. Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities. Science Translational Medicine. 2015;7(303):303ra138. doi: 10.1126/scitranslmed.aaa7582 26333934

24. Gollapalli K, Ghantasala S, Kumar S, Srivastava R, Rapole S, Moiyadi A, et al. Subventricular zone involvement in Glioblastoma—A proteomic evaluation and clinicoradiological correlation. Sci Rep. 2017;7(1):1449. Epub 2017/05/05. doi: 10.1038/s41598-017-01202-8 28469129; PubMed Central PMCID: PMC5431125.

25. Denicolai E, Tabouret E, Colin C, Metellus P, Nanni I, Boucard C, et al. Molecular heterogeneity of glioblastomas; does location matter? Oncotarget. 2015. doi: 10.18632/oncotarget.6433 26637806

26. Jamshidi N, Diehn M, Bredel M, Kuo MD. Illuminating radiogenomic characteristics of glioblastoma multiforme through integration of MR imaging, messenger RNA expression, and DNA copy number variation. Radiology. 2014;270(1):1–2. doi: 10.1148/radiol.13130078 24056404

27. Berendsen S, Varkila M, Kroonen J, Seute T, Snijders TJ, Kauw F, et al. Prognostic relevance of epilepsy at presentation in glioblastoma patients. Neuro-Oncology. 2016;18(5):700–6. Epub 2015/10/01. doi: 10.1093/neuonc/nov238 26420896; PubMed Central PMCID: PMC4827038.

28. Berendsen S, Spliet WGM, Geurts M, Van Hecke W, Seute T, Snijders TJ, et al. Epilepsy Associates with Decreased HIF-1alpha/STAT5b Signaling in Glioblastoma. Cancers. 2019;11(1). Epub 2019/01/10. doi: 10.3390/cancers11010041 30621209.

29. Reich M, Liefeld T, Gould J, Lerner J, Tamayo P, Mesirov JP. GenePattern 2.0. Nature Genetics. 2006;38(5):500–1. doi: 10.1038/ng0506-500 16642009

30. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(43):15545–50. doi: 10.1073/pnas.0506580102 16199517

31. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98–110. doi: 10.1016/j.ccr.2009.12.020 20129251

32. Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, et al. Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals. Nature. 2005;434(7031):338–45. doi: 10.1038/nature03441 15735639

33. Jiang L, Song L, Wu J, Yang Y, Zhu X, Hu B, et al. Bmi-1 promotes glioma angiogenesis by activating NF-kappaB signaling. PLoS One. 2013;8(1):e55527. Epub 2013/02/06. doi: 10.1371/journal.pone.0055527 23383216; PubMed Central PMCID: PMC3561301.

34. Bhat KP, Balasubramaniyan V, Vaillant B, Ezhilarasan R, Hummelink K, Hollingsworth F, et al. Mesenchymal differentiation mediated by NF-kappaB promotes radiation resistance in glioblastoma. Cancer Cell. 2013;24(3):331–46. doi: 10.1016/j.ccr.2013.08.001 23993863

35. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396–401. doi: 10.1038/nature03128 15549107

36. Roelofs RF, Fischer DF, Houtman SH, Sluijs JA, Van Haren W, Van Leeuwen FW, et al. Adult human subventricular, subgranular, and subpial zones contain astrocytes with a specialized intermediate filament cytoskeleton. Glia. 2005;52(4):289–300. doi: 10.1002/glia.20243 16001427

37. Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG, et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. The Lancet Oncology. 2008;9(1):29–38. Epub 2007/12/18. doi: 10.1016/S1470-2045(07)70384-4 18082451.

38. Adeberg S, Bostel T, Konig L, Welzel T, Debus J, Combs SE. A comparison of long-term survivors and short-term survivors with glioblastoma, subventricular zone involvement: a predictive factor for survival? Radiation Oncology (London, England). 2014;9:95–717X-9-95. doi: 10.1186/1748-717X-9-95 24758192

39. Matsuda M, Kohzuki H, Ishikawa E, Yamamoto T, Akutsu H, Takano S, et al. Prognostic analysis of patients who underwent gross total resection of newly diagnosed glioblastoma. J Clin Neurosci. 2018;50:172–6. Epub 2018/02/06. doi: 10.1016/j.jocn.2018.01.009 29396060.

40. Nakagawa Y, Sasaki H, Ohara K, Ezaki T, Toda M, Ohira T, et al. Clinical and Molecular Prognostic Factors for Long-Term Survival of Patients with Glioblastomas in Single-Institutional Consecutive Cohort. World Neurosurg. 2017;106:165–73. Epub 2017/07/02. doi: 10.1016/j.wneu.2017.06.126 28666913.

41. Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S. Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro-Oncology. 2013;15(1):91–6. Epub 2012/10/26. doi: 10.1093/neuonc/nos268 23095230; PubMed Central PMCID: PMC3534420.

42. Young GS, Macklin EA, Setayesh K, Lawson JD, Wen PY, Norden AD, et al. Longitudinal MRI evidence for decreased survival among periventricular glioblastoma. Journal of Neuro-Oncology. 2011;104(1):261–9. doi: 10.1007/s11060-010-0477-1 21132516

43. Mistry AM, Dewan MC, White-Dzuro GA, Brinson PR, Weaver KD, Thompson RC, et al. Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum. Journal of Neuro-Oncology. 2017;132(2):341–9. Epub 2017/01/12. doi: 10.1007/s11060-017-2374-3 28074322; PubMed Central PMCID: PMC5771712.

44. Weinberg BD, Boreta L, Braunstein S, Cha S. Location of subventricular zone recurrence and its radiation dose predicts survival in patients with glioblastoma. Journal of Neuro-Oncology. 2018;138(3):549–56. Epub 2018/03/17. doi: 10.1007/s11060-018-2822-8 29546530.

45. Woo P, Ho J, Lam S, Ma E, Chan D, Wong WK, et al. A Comparative Analysis of the Usefulness of Survival Prediction Models for Patients with Glioblastoma in the Temozolomide Era: The Importance of Methylguanine Methyltransferase Promoter Methylation, Extent of Resection, and Subventricular Zone Location. World Neurosurg. 2018;115:e375–e85. Epub 2018/04/22. doi: 10.1016/j.wneu.2018.04.059 29678708.

46. Mistry AM, Wooten DJ, Davis LT, Mobley BC, Quaranta V, Ihrie RA. Ventricular-Subventricular Zone Contact by Glioblastoma is Not Associated with Molecular Signatures in Bulk Tumor Data. Sci Rep. 2019;9(1):1842. Epub 2019/02/14. doi: 10.1038/s41598-018-37734-w 30755636; PubMed Central PMCID: PMC6372607.

47. Mistry AM. Clinical correlates of subventricular zone-contacting glioblastomas: a meta-analysis. Journal of Neurosurgical Sciences. 2017. doi: 10.23736/S0390-5616.17.04274–6

48. Harat M, Malkowski B, Roszkowski K. Prognostic value of subventricular zone involvement in relation to tumor volumes defined by fused MRI and O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) PET imaging in glioblastoma multiforme. Radiation Oncology (London, England). 2019;14(1):37. Epub 2019/03/06. doi: 10.1186/s13014-019-1241-0 30832691; PubMed Central PMCID: PMC6398237.

49. Kongkham PN, Knifed E, Tamber MS, Bernstein M. Complications in 622 cases of frame-based stereotactic biopsy, a decreasing procedure. The Canadian Journal of Neurological Sciences. 2008;35(1):79–84. doi: 10.1017/s0317167100007605 18380282

50. Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS. An extent of resection threshold for newly diagnosed glioblastomas. Journal of Neurosurgery. 2011;115(1):3–8. doi: 10.3171/2011.2.JNS10998 21417701

51. Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL, et al. Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis. JAMA Oncology. 2016;2(11):1460–9. Epub 2016/06/17. doi: 10.1001/jamaoncol.2016.1373 27310651.

52. Steed TC, Treiber JM, Patel K, Ramakrishnan V, Merk A, Smith AR, et al. Differential localization of glioblastoma subtype: implications on glioblastoma pathogenesis. Oncotarget. 2016;7(18):24899–907. doi: 10.18632/oncotarget.8551 27056901

53. Carro MS, Lim WK, Alvarez MJ, Bollo RJ, Zhao X, Snyder EY, et al. The transcriptional network for mesenchymal transformation of brain tumours. Nature. 2010;463(7279):318–25. Epub 2009/12/25. doi: 10.1038/nature08712 20032975; PubMed Central PMCID: PMC4011561.

54. Cooper LA, Gutman DA, Chisolm C, Appin C, Kong J, Rong Y, et al. The tumor microenvironment strongly impacts master transcriptional regulators and gene expression class of glioblastoma. The American Journal of Pathology. 2012;180(5):2108–19. Epub 2012/03/24. doi: 10.1016/j.ajpath.2012.01.040 22440258; PubMed Central PMCID: PMC3354586.

55. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathologica. 2007;114(2):97–109. Epub 2007/07/10. doi: 10.1007/s00401-007-0243-4 17618441; PubMed Central PMCID: PMC1929165.

56. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathologica. 2016;131(6):803–20. Epub 2016/05/10. doi: 10.1007/s00401-016-1545-1 27157931.