Liquid biopsies in patients with diffuse glioma

Acta Neuropathologica

Volumn 129, Issue 6, 2015, Pages 849-865

  Best, Myron G ^a   Sol, Nik ^a   Zijl, Sebastiaan ^a   Reijneveld, Jaap C ^a   Wesseling, Pieter ^a,b   Wurdinger, Thomas ^a,c,d  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d ThromboDX BV   (Netherlands)

Author keywords

Liquid biopsies; Malignant glioma; Minimally invasive biomarkers; Molecular diagnostics

Indexed keywords

CIRCULATING NUCLEIC ACID; CIRCULATING PROTEIN; MOLECULAR MARKER; NUCLEIC ACID; PROTEIN; UNCLASSIFIED DRUG; TUMOR MARKER;

BRAIN BIOPSY; CANCER DIAGNOSIS; CANCER PROGNOSIS; CEREBROSPINAL FLUID ANALYSIS; CIRCULATING TUMOR CELL; CLINICAL TRIAL (TOPIC); GLIOMA; HUMAN; LIQUID BIOPSY; PRIORITY JOURNAL; REVIEW; TUMOR BIOPSY; BIOPSY; BRAIN NEOPLASMS; METABOLISM; PROCEDURES;

BIOMARKERS, TUMOR; BIOPSY; BRAIN NEOPLASMS; GLIOMA; HUMANS;

EID: 84929706385     PISSN: 00016322     EISSN: 14320533     Source Type: Journal    
DOI: 10.1007/s00401-015-1399-y     Document Type: Review

References (195)

1. Akers JC, Ramakrishnan V, Kim R, Skog J, Nakano I, Pingle S, Kalinina J, Hua W, Kesari S, Mao Y, Breakefield XO, Hochberg FH, Van Meir EG, Carter BS, Chen CC (2013) MiR-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF): a platform for glioblastoma biomarker development. PLoS One 8:e78115. doi:10.1371/journal.pone.0078115
2. Albulescu R, Codrici E, Popescu ID, Mihai S, Necula LG, Petrescu D, Teodoru M, Tanase CP (2013) Cytokine patterns in brain tumour progression. Mediators Inflamm 2013:979748. doi:10.1155/2013/979748
3. Alix-Panabières C, Pantel K (2013) Circulating tumor cells: liquid biopsy of cancer. Clin Chem 59:110–118. doi:10.1373/clinchem.2012.194258
4. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, Rak J (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10:619–624. doi:10.1038/ncb1725
5. El Andaloussi A, Lesniak MS (2006) An increase in CD4+ CD25+ FOXP3+ regulatory T cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme. Neuro Oncol 8:234–243. doi:10.1215/15228517-2006-006
6. Babu R, Adamson DC (2012) Rindopepimut: an evidence-based review of its therapeutic potential in the treatment of EGFRvIII-positive glioblastoma. Core Evid 7:93–103. doi:10.2147/CE.S29001
7. Bailey P (1926) A classification of the tumors of the glioma group on a histogenetic basis with a correlated study of prognosis. Lippincott, Philadelphia
8. Balaña C, Ramirez JL, Taron M, Roussos Y, Ariza A, Ballester R, Sarries C, Mendez P, Sanchez JJ, Rosell R (2003) O6-methyl-guanine-DNA methyltransferase methylation in serum and tumor DNA predicts response to 1,3-bis(2-chloroethyl)-1-nitrosourea but not to temozolamide plus cisplatin in glioblastoma multiforme. Clin Cancer Res 9:1461–1468
9. Baldock AL, Yagle K, Born DE, Ahn S, Trister AD, Neal M, Johnston SK, Bridge CA, Basanta D, Scott J, Malone H, Sonabend AM, Canoll P, Mrugala MM, Rockhill JK, Rockne RC, Swanson KR (2014) Invasion and proliferation kinetics in enhancing gliomas predict IDH1 mutation status. Neuro Oncol 16:779–786. doi:10.1093/neuonc/nou027
10. Baraniskin A, Kuhnhenn J, Schlegel U, Maghnouj A, Zöllner H, Schmiegel W, Hahn S, Schroers R (2012) Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. Neuro Oncol 14:29–33. doi:10.1093/neuonc/nor169
11. Batchelor TT, Duda DG, di Tomaso E, Ancukiewicz M, Plotkin SR, Gerstner E, Eichler AF, Drappatz J, Hochberg FH, Benner T, Louis DN, Cohen KS, Chea H, Exarhopoulos A, Loeffler JS, Moses MA, Ivy P, Sorensen AG, Wen PY et al (2010) Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 28:2817–2823. doi:10.1200/JCO.2009.26.3988
12. Batchelor TT, Gerstner ER, Emblem KE, Duda DG, Kalpathy-Cramer J, Snuderl M, Ancukiewicz M, Polaskova P, Pinho MC, Jennings D, Plotkin SR, Chi AS, Eichler AF, Dietrich J, Hochberg FH, Lu-Emerson C, Iafrate AJ, Ivy SP, Rosen BR et al (2013) Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation. Proc Natl Acad Sci 110:19059–19064. doi:10.1073/pnas.1318022110
13. Batchelor TT, Sorensen AG, di Tomaso E, Zhang W-T, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen P-J, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loeffler JS et al (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83–95. doi:10.1016/j.ccr.2006.11.021
14. Beiko J, Suki D, Hess KR, Fox BD, Cheung V, Cabral M, Shonka N, Gilbert MR, Sawaya R, Prabhu SS, Weinberg J, Lang FF, Aldape KD, Sulman EP, Rao G, McCutcheon IE, Cahill DP (2014) IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro Oncol 16:81–91. doi:10.1093/neuonc/not159
15. Bernardi D, Padoan A, Ballin A, Sartori M, Manara R, Scienza R, Plebani M, Della Puppa A (2012) Serum YKL-40 following resection for cerebral glioblastoma. J Neurooncol 107:299–305. doi:10.1007/s11060-011-0762-7
16. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P et al (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6:224ra24. doi:10.1126/scitranslmed.3007094
17. Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6:131–144. doi:10.1038/nrneurol.2010.4
18. Böhm C, Wassmann H, Paulus W (2003) No evidence of tumour cells in blood of patients with glioma. Mol Pathol 56:187–189
19. Boisselier B, Gállego Pérez-Larraya J, Rossetto M, Labussière M, Ciccarino P, Marie Y, Delattre J-Y, Sanson M (2012) Detection of IDH1 mutation in the plasma of patients with glioma. Neurology 79:1693–1698. doi:10.1212/WNL.0b013e31826e9b0a
20. De Bont JM, den Boer ML, Reddingius RE, Jansen J, Passier M, van Schaik RHN, Kros JM, Sillevis Smitt PA, Luider TH, Pieters R (2006) Identification of apolipoprotein A-II in cerebrospinal fluid of pediatric brain tumor patients by protein expression profiling. Clin Chem 52:1501–1509. doi:10.1373/clinchem.2006.069294
21. Brandes AA, Basso U, Reni M, Vastola F, Tosoni A, Cavallo G, Scopece L, Ferreri AJ, Panucci MG, Monfardini S, Ermani M (2004) First-line chemotherapy with cisplatin plus fractionated temozolomide in recurrent glioblastoma multiforme: a phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia. J Clin Oncol 22:1598–1604. doi:10.1200/JCO.2004.11.019
22. Brennan CW, Verhaak RGW, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, Beroukhim R, Bernard B, Wu C-J, Genovese G, Shmulevich I, Barnholtz-Sloan J, Zou L, Vegesna R, Shukla SA et al (2013) The somatic genomic landscape of glioblastoma. Cell 155:462–477. doi:10.1016/j.cell.2013.09.034
23. Brinker T, Stopa E, Morrison J, Klinge P (2014) A new look at cerebrospinal fluid circulation. Fluids Barriers CNS 11:10. doi:10.1186/2045-8118-11-10
24. Brommeland T, Rosengren L, Fridlund S, Hennig R, Isaksen V (2007) Serum levels of glial fibrillary acidic protein correlate to tumour volume of high-grade gliomas. Acta Neurol Scand 116:380–384. doi:10.1111/j.1600-0404.2007.00889.x
25. Bush MA, Samara E, Whitehouse MJ, Yoshizawa C, Novicki DL, Pike M, Laham RJ, Simons M, Chronos NA (2001) Pharmacokinetics and pharmacodynamics of recombinant FGF-2 in a phase I trial in coronary artery disease. J Clin Pharmacol 41:378–385
26. Campos S, Davey P, Hird A, Pressnail B, Bilbao J, Aviv RI, Symons S, Pirouzmand F, Sinclair E, Culleton S, Desa E, Goh P, Chow E (2009) Brain metastasis from an unknown primary, or primary brain tumour? A diagnostic dilemma. Curr Oncol 16:62–66
27. Capper D, Simon M, Langhans C-D, Okun JG, Tonn JC, Weller M, von Deimling A, Hartmann C (2012) 2-Hydroxyglutarate concentration in serum from patients with gliomas does not correlate with IDH1/2 mutation status or tumor size. Int J Cancer 131:766–768. doi:10.1002/ijc.26425
28. Carlsson A, Persson O, Ingvarsson J, Widegren B, Salford L, Borrebaeck CAK, Wingren C (2010) Plasma proteome profiling reveals biomarker patterns associated with prognosis and therapy selection in glioblastoma multiforme patients. Proteomics Clin Appl 4:591–602. doi:10.1002/prca.200900173
29. Carson KA, Grossman SA, Fisher JD, Shaw EG (2007) Prognostic factors for survival in adult patients with recurrent glioma enrolled onto the new approaches to brain tumor therapy CNS consortium phase I and II clinical trials. J Clin Oncol 25:2601–2606. doi:10.1200/JCO.2006.08.1661
30. Chen C, Skog J, Hsu C-H, Lessard RT, Balaj L, Wurdinger T, Carter BS, Breakefield XO, Toner M, Irimia D (2010) Microfluidic isolation and transcriptome analysis of serum microvesicles. Lab Chip 10:505–511. doi:10.1039/b916199f
31. Chen J, Gong M, Lu S, Liu F, Xia L, Nie D, Zou F, Shi J, Ju S, Zhao L, Zuo H, Qi J, Shi W (2013) Detection of serum Alu element hypomethylation for the diagnosis and prognosis of glioma. J Mol Neurosci 50:368–375. doi:10.1007/s12031-013-0014-8
32. Chen WW, Balaj L, Liau LM, Samuels ML, Kotsopoulos SK, Maguire CA, Loguidice L, Soto H, Garrett M, Zhu LD, Sivaraman S, Chen C, Wong ET, Carter BS, Hochberg FH, Breakefield XO, Skog J (2013) BEAMing and droplet digital PCR analysis of mutant IDH1 mRNA in glioma patient serum and cerebrospinal fluid extracellular vesicles. Mol Ther Nucleic Acids 2:e109. doi:10.1038/mtna.2013.28
33. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006. doi:10.1038/cr.2008.282
34. Chinnaiyan P, Chowdhary S, Potthast L, Prabhu A, Tsai Y-Y, Sarcar B, Kahali S, Brem S, Yu HM, Rojiani A, Murtagh R, Pan E (2012) Phase I trial of vorinostat combined with bevacizumab and CPT-11 in recurrent glioblastoma. Neuro Oncol 14:93–100. doi:10.1093/neuonc/nor187
35. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709–722. doi:10.1056/NEJMoa1308345
36. Claes A, Idema AJ, Wesseling P (2007) Diffuse glioma growth: a guerilla war. Acta Neuropathol 114:443–458. doi:10.1007/s00401-007-0293-7
37. Corsini E, Ciusani E, Gaviani P, Silvani A, Canazza A, Bernardi G, Calatozzolo C, DiMeco F, Di Meco F, Salmaggi A (2012) Decrease in circulating endothelial progenitor cells in treated glioma patients. J Neurooncol 108:123–129. doi:10.1007/s11060-012-0805-8
38. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA (2011) MicroRNAs in body fluids–the mix of hormones and biomarkers. Nat Rev Clin Oncol 8:467–477. doi:10.1038/nrclinonc.2011.76
39. Crocker M, Ashley S, Giddings I, Petrik V, Hardcastle A, Aherne W, Pearson A, Bell BA, Zacharoulis S, Papadopoulos MC (2011) Serum angiogenic profile of patients with glioblastoma identifies distinct tumor subtypes and shows that TIMP-1 is a prognostic factor. Neuro Oncol 13:99–108. doi:10.1093/neuonc/noq170
40. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A (2013) Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 10:472–484. doi:10.1038/nrclinonc.2013.110
41. Cuddapah VA, Robel S, Watkins S, Sontheimer H (2014) A neurocentric perspective on glioma invasion. Nat Rev Neurosci 15:455–465. doi:10.1038/nrn3765
42. Cuppini L, Calleri A, Bruzzone MG, Prodi E, Anghileri E, Pellegatta S, Mancuso P, Porrati P, Di Stefano AL, Ceroni M, Bertolini F, Finocchiaro G, Eoli M (2013) Prognostic value of CD109+ circulating endothelial cells in recurrent glioblastomas treated with bevacizumab and irinotecan. PLoS One 8:e74345. doi:10.1371/journal.pone.0074345
43. D’Souza-Schorey C, Clancy JW (2012) Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes Dev 26:1287–1299. doi:10.1101/gad.192351.112
44. Dawson S-J, Tsui DWY, Murtaza M, Biggs H, Rueda OM, Chin S-F, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C, Rosenfeld N (2013) Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368:1199–1209. doi:10.1056/NEJMoa1213261
45. Elstner A, Stockhammer F, Nguyen-Dobinsky T-N, Nguyen QL, Pilgermann I, Gill A, Guhr A, Zhang T, von Eckardstein K, Picht T, Veelken J, Martuza RL, von Deimling A, Kurtz A (2011) Identification of diagnostic serum protein profiles of glioblastoma patients. J Neurooncol 102:71–80. doi:10.1007/s11060-010-0284-8
46. Eoli M, Di Stefano A, Aquino D, Scotti A, Anghileri E, Cuppini L, Prodi E, Finocchiaro G, Bruzzone MG (2013) MC13-0072 Tumor perfusion during bevacizumab and irinotecan in recurrent glioblastoma: a multimodal approach. Eur J Cancer 49:S32. doi:10.1016/S0959-8049(13)70179-5
47. Fecci PE, Mitchell DA, Whitesides JF, Xie W, Friedman AH, Archer GE, Herndon JE, Bigner DD, Dranoff G, Sampson JH (2006) Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res 66:3294–3302. doi:10.1158/0008-5472.CAN-05-3773
48. Fiano V, Trevisan M, Trevisan E, Senetta R, Castiglione A, Sacerdote C, Gillio-Tos A, De Marco L, Grasso C, Magistrello M, Tondat F, Rudà R, Cassoni P, Soffietti R, Merletti F (2014) MGMT promoter methylation in plasma of glioma patients receiving temozolomide. J Neurooncol 117:347–357. doi:10.1007/s11060-014-1395-4
49. Fine HA, Figg WD, Jaeckle K, Wen PY, Kyritsis AP, Loeffler JS, Levin VA, Black PM, Kaplan R, Pluda JM, Yung WK (2000) Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol 18:708–715
50. Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DWY, Kaper F, Dawson S-J, Piskorz AM, Jimenez-Linan M, Bentley D, Hadfield J, May AP, Caldas C, Brenton JD, Rosenfeld N (2012) Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med 4:136ra68. doi:10.1126/scitranslmed.3003726
51. Friedberg MH, Glantz MJ, Klempner MS, Cole BF, Perides G (1998) Specific matrix metalloproteinase profiles in the cerebrospinal fluid correlated with the presence of malignant astrocytomas, brain metastases, and carcinomatous meningitis. Cancer 82:923–930
52. Gállego Pérez-Larraya J, Paris S, Idbaih A, Dehais C, Laigle-Donadey F, Navarro S, Capelle L, Mokhtari K, Marie Y, Sanson M, Hoang-Xuan K, Delattre J-Y, Mallet A (2014) Diagnostic and prognostic value of preoperative combined GFAP, IGFBP-2, and YKL-40 plasma levels in patients with glioblastoma. Cancer. doi:10.1002/cncr.28949
53. Garcia-Navarrete R, Garcia E, Arrieta O, Sotelo J (2010) Hepatocyte growth factor in cerebrospinal fluid is associated with mortality and recurrence of glioblastoma, and could be of prognostic value. J Neurooncol 97:347–351. doi:10.1007/s11060-009-0037-8
54. Garnier D, Jabado N, Rak J (2013) Extracellular vesicles as prospective carriers of oncogenic protein signatures in adult and paediatric brain tumours. Proteomics 13:1595–1607. doi:10.1002/pmic.201200360
55. Gautam P, Nair SC, Gupta MK, Sharma R, Polisetty RV, Uppin MS, Sundaram C, Puligopu AK, Ankathi P, Purohit AK, Chandak GR, Harsha HC, Sirdeshmukh R (2012) Proteins with altered levels in plasma from glioblastoma patients as revealed by iTRAQ-based quantitative proteomic analysis. PLoS One 7:e46153. doi:10.1371/journal.pone.0046153
56. Gerstner ER, Eichler AF, Plotkin SR, Drappatz J, Doyle CL, Xu L, Duda DG, Wen PY, Jain RK, Batchelor TT (2011) Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and standard radiation and temozolomide. J Neurooncol 103:325–332. doi:10.1007/s11060-010-0390-7
57. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP et al (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370:699–708. doi:10.1056/NEJMoa1308573
58. Gorlia T, Stupp R, Brandes AA, Rampling RR, Fumoleau P, Dittrich C, Campone MM, Twelves CC, Raymond E, Hegi ME, Lacombe D, van den Bent MJ (2012) New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials. Eur J Cancer 48:1176–1184. doi:10.1016/j.ejca.2012.02.004
59. Gousias K, Markou M, Arzoglou V, Voulgaris S, Vartholomatos G, Kostoula A, Voulgari P, Polyzoidis K, Kyritsis AP (2010) Frequent abnormalities of the immune system in gliomas and correlation with the WHO grading system of malignancy. J Neuroimmunol 226:136–142. doi:10.1016/j.jneuroim.2010.05.027
60. Gousias K, von Ruecker A, Voulgari P, Simon M (2013) Phenotypical analysis, relation to malignancy and prognostic relevance of ICOS+ T regulatory and dendritic cells in patients with gliomas. J Neuroimmunol 264:84–90. doi:10.1016/j.jneuroim.2013.09.001
61. Greenfield JP, Jin DK, Young LM, Christos PJ, Abrey L, Rafii S, Gutin PH (2009) Surrogate markers predict angiogenic potential and survival in patients with glioblastoma multiforme. Neurosurgery 64:819–826. doi:10.1227/01.NEU.0000343742.06625.DB (discussion 826–827)
62. De Groot JF, Piao Y, Tran H, Gilbert M, Wu H-K, Liu J, Bekele BN, Cloughesy T, Mehta M, Robins HI, Lassman A, DeAngelis L, Camphausen K, Chen A, Yung W, Prados M, Wen PY, Heymach JV (2011) Myeloid biomarkers associated with glioblastoma response to anti-VEGF therapy with aflibercept. Clin Cancer Res 17:4872–4881. doi:10.1158/1078-0432.CCR-11-0271
63. Güttler A, Giebler M, Cuno P, Wichmann H, Keßler J, Ostheimer C, Söling A, Strauss C, Illert J, Kappler M, Vordermark D, Bache M (2013) Osteopontin and splice variant expression level in human malignant glioma: radiobiologic effects and prognosis after radiotherapy. Radiother Oncol 108:535–540. doi:10.1016/j.radonc.2013.06.036
64. Hegi ME, Diserens A-C, Gorlia T, Hamou M-F, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JEC, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003. doi:10.1056/NEJMoa043331
65. Hoke M, Dieckmann K, Koppensteiner R, Schillinger M, Marosi C, Mlekusch W (2011) Prognostic value of plasma d-dimer levels in patients with glioblastoma multiforme—results from a pilot study. Wien Klin Wochenschr 123:199–203. doi:10.1007/s00508-011-1556-9
66. Holdhoff M, Yovino SG, Boadu O, Grossman SA (2013) Blood-based biomarkers for malignant gliomas. J Neurooncol 113:345–352. doi:10.1007/s11060-013-1144-0
67. Hormigo A, Gu B, Karimi S, Riedel E, Panageas KS, Edgar MA, Tanwar MK, Rao JS, Fleisher M, DeAngelis LM, Holland EC (2006) YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas. Clin Cancer Res 12:5698–5704. doi:10.1158/1078-0432.CCR-06-0181
68. Husain H, Savage W, Grossman SA, Ye X, Burger PC, Everett A, Bettegowda C, Diaz LA, Blair C, Romans KE, Holdhoff M (2012) Pre- and post-operative plasma glial fibrillary acidic protein levels in patients with newly diagnosed gliomas. J Neurooncol 109:123–127. doi:10.1007/s11060-012-0874-8
69. Huttner HB, Janich P, Köhrmann M, Jászai J, Siebzehnrubl F, Blümcke I, Suttorp M, Gahr M, Kuhnt D, Nimsky C, Krex D, Schackert G, Löwenbrück K, Reichmann H, Jüttler E, Hacke W, Schellinger PD, Schwab S, Wilsch-Bräuninger M et al (2008) The stem cell marker prominin-1/CD133 on membrane particles in human cerebrospinal fluid offers novel approaches for studying central nervous system disease. Stem Cells 26:698–705. doi:10.1634/stemcells.2007-0639
70. Idbaih A, Omuro A, Ducray F, Hoang-Xuan K (2007) Molecular genetic markers as predictors of response to chemotherapy in gliomas. Curr Opin Oncol 19:606–611. doi:10.1097/CCO.0b013e3282f075f3
71. Ilhan A, Gartner W, Neziri D, Czech T, Base W, Hörl WH, Wagner L (2009) Angiogenic factors in plasma of brain tumour patients. Anticancer Res 29:731–736
72. Ilhan-Mutlu A, Wagner L, Preusser M (2013) Circulating biomarkers of CNS tumors: an update. Biomark Med 7:267–285. doi:10.2217/bmm.13.12
73. Ilhan-Mutlu A, Wagner L, Widhalm G, Wöhrer A, Bartsch S, Czech T, Heinzl H, Leutmezer F, Prayer D, Marosi C, Base W, Preusser M (2013) Exploratory investigation of eight circulating plasma markers in brain tumor patients. Neurosurg Rev 36:45–55. doi:10.1007/s10143-012-0401-6 (discussion 55–56)
74. Ilhan-Mutlu A, Wagner L, Wöhrer A, Furtner J, Widhalm G, Marosi C, Preusser M (2012) Plasma MicroRNA-21 concentration may be a useful biomarker in glioblastoma patients. Cancer Invest 30:615–621. doi:10.3109/07357907.2012.708071
75. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 4:147ra111. doi:10.1126/scitranslmed.3003748
76. Iwadate Y, Hayama M, Adachi A, Matsutani T, Nagai Y, Hiwasa T, Saeki N (2008) High serum level of plasminogen activator inhibitor-1 predicts histological grade of intracerebral gliomas. Anticancer Res 28:415–418
77. Iwamoto FM, Hottinger AF, Karimi S, Riedel E, Dantis J, Jahdi M, Panageas KS, Lassman AB, Abrey LE, Fleisher M, DeAngelis LM, Holland EC, Hormigo A (2011) Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas. Neuro Oncol 13:1244–1251. doi:10.1093/neuonc/nor117
78. Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS, Batchelor TT, Sorensen AG (2009) Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 6:327–338. doi:10.1038/nrclinonc.2009.63
79. Jelkmann W (2001) Pitfalls in the measurement of circulating vascular endothelial growth factor. Clin Chem 47:617–623
80. Jung CS, Foerch C, Schänzer A, Heck A, Plate KH, Seifert V, Steinmetz H, Raabe A, Sitzer M (2007) Serum GFAP is a diagnostic marker for glioblastoma multiforme. Brain 130:3336–3341. doi:10.1093/brain/awm263
81. Khleif SN, Doroshow JH, Hait WN (2010) AACR-FDA-NCI cancer biomarkers collaborative consensus report: advancing the use of biomarkers in cancer drug development. Clin Cancer Res 16:3299–3318. doi:10.1158/1078-0432.CCR-10-0880
82. Khwaja FW, Nolen JDL, Mendrinos SE, Lewis MM, Olson JJ, Pohl J, Van Meir EG, Ritchie JC, Brat DJ (2006) Proteomic analysis of cerebrospinal fluid discriminates malignant and nonmalignant disease of the central nervous system and identifies specific protein markers. Proteomics 6:6277–6287. doi:10.1002/pmic.200600135
83. Khwaja FW, Reed MS, Olson JJ, Schmotzer BJ, Gillespie GY, Guha A, Groves MD, Kesari S, Pohl J, Van Meir EG (2007) Proteomic identification of biomarkers in the cerebrospinal fluid (CSF) of astrocytoma patients. J Proteome Res 6:559–570. doi:10.1021/pr060240z
84. Kikuchi K, Gotoh H, Kowada M (1987) Immunosuppressive acidic protein in patients with brain tumours: a preliminary report. Acta Neurochir (Wien) 86:42–49. doi:10.1007/BF01419503
85. Klement GL, Yip T-T, Cassiola F, Kikuchi L, Cervi D, Podust V, Italiano JE, Wheatley E, Abou-Slaybi A, Bender E, Almog N, Kieran MW, Folkman J (2009) Platelets actively sequester angiogenesis regulators. Blood 113:2835–2842. doi:10.1182/blood-2008-06-159541
86. Koppers-Lalic D, Hackenberg M, Bijnsdorp IV, van Eijndhoven MAJ, Sadek P, Sie D, Zini N, Middeldorp JM, Ylstra B, de Menezes RX, Würdinger T, Meijer GA, Pegtel DM (2014) Nontemplated nucleotide additions distinguish the small rna composition in cells from exosomes. Cell Rep. 8:1–10. doi:10.1016/j.celrep.2014.08.027
87. Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C (2014) Molecular analysis of circulating tumour cells-biology and biomarkers. Nat Rev Clin Oncol 11:129–144. doi:10.1038/nrclinonc.2013.253
88. Kros JM, Mustafa DM, Dekker LJM, Sillevis Smitt PAE, Luider TM, Zheng P-P (2014) Circulating glioma biomarkers. Neuro Oncol. doi:10.1093/neuonc/nou207
89. Kumar DM, Thota B, Shinde SV, Prasanna KV, Hegde AS, Arivazhagan A, Chandramouli BA, Santosh V, Somasundaram K (2010) Proteomic identification of haptoglobin α2 as a glioblastoma serum biomarker: implications in cancer cell migration and tumor growth. J Proteome Res 9:5557–5567. doi:10.1021/pr1001737
90. Kuratsu J, Yoshizato K, Yoshimura T, Leonard EJ, Takeshima H, Ushio Y (1993) Quantitative study of monocyte chemoattractant protein-1 (MCP-1) in cerebrospinal fluid and cyst fluid from patients with malignant glioma. J Natl Cancer Inst 85:1836–1839
91. Lange RP, Everett A, Dulloor P, Korley FK, Bettegowda C, Blair C, Grossman SA, Holdhoff M (2014) Evaluation of eight plasma proteins as candidate blood-based biomarkers for malignant gliomas. Cancer Invest 32:423–429. doi:10.3109/07357907.2014.933237
92. Lavon I, Refael M, Zelikovitch B, Shalom E, Siegal T (2010) Serum DNA can define tumor-specific genetic and epigenetic markers in gliomas of various grades. Neuro Oncol 12:173–180. doi:10.1093/neuonc/nop041
93. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ (1977) Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 37:646–650
94. Lin Y, Jiang T, Zhou K, Xu L, Chen B, Li G, Qiu X, Jiang T, Zhang W, Song SW (2009) Plasma IGFBP-2 levels predict clinical outcomes of patients with high-grade gliomas. Neuro Oncol 11:468–476. doi:10.1215/15228517-2008-114
95. Lin Y, Wang J-F, Gao G-Z, Zhang G-Z, Wang F-L, Wang Y-J (2013) Plasma levels of tissue inhibitor of matrix metalloproteinase-1 correlate with diagnosis and prognosis of glioma patients. Chin Med J (Engl) 126:4295–4300
96. Liu B-L, Cheng J-X, Zhang W, Zhang X, Wang R, Lin H, Huo J-L, Cheng H (2010) Quantitative detection of multiple gene promoter hypermethylation in tumor tissue, serum, and cerebrospinal fluid predicts prognosis of malignant gliomas. Neuro Oncol 12:540–548. doi:10.1093/neuonc/nop064
97. Locasale JW, Melman T, Song S, Yang X, Swanson KD, Cantley LC, Wong ET, Asara JM (2012) Metabolomics of human cerebrospinal fluid identifies signatures of malignant glioma. Mol Cell Proteomics 11(M111):014688. doi:10.1074/mcp.M111.014688
98. Lombardi G, Corona G, Farina P, Pambuku A, Bellu L, Della Puppa A, Fiduccia P, Bertorelle R, Paola Gardiman M, Toffoli GZV (2014) Diagnostic value of plasma and urinary 2-hydroxyglutarate to identify patients with IDH-mutated glioma. J Clin Oncol 32:5s (suppl; abstr 2037)
99. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109. doi:10.1007/s00401-007-0243-4
100. Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, von Deimling A, Aldape K, Brat D, Collins VP, Eberhart C, Figarella-Branger D, Fuller GN, Giangaspero F, Giannini C, Hawkins C, Kleihues P, Korshunov A, Kros JM, Beatriz Lopes M et al (2014) International Society of Neuropathology–Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 24:429–435. doi:10.1111/bpa.12171
101. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system. IARC Press, Lyon
102. Lyubimova NV, Toms MG, Popova EE, Bondarenko YV, Krat VB, Kushlinskii NE (2011) Neurospecific proteins in the serum of patients with brain tumors. Bull Exp Biol Med 150:732–734
103. Ma R, Zhang G, Wang H, Lv H, Fang F, Kang X (2012) Downregulation of miR-544 in tissue, but not in serum, is a novel biomarker of malignant transformation in glioma. Oncol Lett 4:1321–1324. doi:10.3892/ol.2012.918
104. Macarthur KM, Kao GD, Chandrasekaran S, Alonso-Basanta M, Chapman C, Lustig RA, Wileyto EP, Hahn SM, Dorsey JF (2014) Detection of brain tumor cells in the peripheral blood by a telomerase promoter-based assay. Cancer Res 74:2152–2159. doi:10.1158/0008-5472.CAN-13-0813
105. Majchrzak-Celińska A, Paluszczak J, Kleszcz R, Magiera M, Barciszewska A-M, Nowak S, Baer-Dubowska W (2013) Detection of MGMT, RASSF1A, p15INK4B, and p14ARF promoter methylation in circulating tumor-derived DNA of central nervous system cancer patients. J Appl Genet 54:335–344. doi:10.1007/s13353-013-0149-x
106. Manterola L, Guruceaga E, Gállego Pérez-Larraya J, González-Huarriz M, Jauregui P, Tejada S, Diez-Valle R, Segura V, Samprón N, Barrena C, Ruiz I, Agirre A, Ayuso A, Rodríguez J, González A, Xipell E, Matheu A, López de Munain A, Tuñón T et al (2014) A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool. Neuro Oncol 16:520–527. doi:10.1093/neuonc/not218
107. Martens T, Matschke J, Müller C, Riethdorf S, Balabanov S, Westphal M, Heese O (2013) Skeletal spread of an anaplastic astrocytoma (WHO grade III) and preservation of histopathological properties within metastases. Clin Neurol Neurosurg 115:323–328. doi:10.1016/j.clineuro.2012.05.025
108. Martin-Villalba A, Okuducu AF, von Deimling A (2008) The evolution of our understanding on glioma. Brain Pathol 18:455–463. doi:10.1111/j.1750-3639.2008.00136.x
109. Masui K, Cloughesy TF, Mischel PS (2012) Review: molecular pathology in adult high-grade gliomas: from molecular diagnostics to target therapies. Neuropathol Appl Neurobiol 38:271–291. doi:10.1111/j.1365-2990.2011.01238.x
110. Matsuura H, Nakazawa S (1985) Prognostic significance of serum alpha 1-acid glycoprotein in patients with glioblastoma multiforme: a preliminary communication. J Neurol Neurosurg Psychiatry 48:835–837
111. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci 105:10513–10518. doi:10.1073/pnas.0804549105
112. Møller HG, Rasmussen AP, Andersen HH, Johnsen KB, Henriksen M, Duroux M (2013) A systematic review of microRNA in glioblastoma multiforme: micro-modulators in the mesenchymal mode of migration and invasion. Mol Neurobiol 47:131–144. doi:10.1007/s12035-012-8349-7
113. Muller C, Holtschmidt J, Auer M, Heitzer E, Lamszus K, Schulte A, Matschke J, Langer-Freitag S, Gasch C, Stoupiec M, Mauermann O, Peine S, Glatzel M, Speicher MR, Geigl JB, Westphal M, Pantel K, Riethdorf S (2014) Hematogenous dissemination of glioblastoma multiforme. Sci Transl Med 6:247ra101. doi:10.1126/scitranslmed.3009095
114. Murtaza M, Dawson S-J, Tsui DWY, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin S-F, Kingsbury Z, Wong ASC, Marass F, Humphray S, Hadfield J, Bentley D, Chin TM, Brenton JD, Caldas C, Rosenfeld N (2013) Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497:108–112. doi:10.1038/nature12065
115. Nakamizo S, Sasayama T, Shinohara M, Irino Y, Nishiumi S, Nishihara M, Tanaka H, Tanaka K, Mizukawa K, Itoh T, Taniguchi M, Hosoda K, Yoshida M, Kohmura E (2013) GC/MS-based metabolomic analysis of cerebrospinal fluid (CSF) from glioma patients. J Neurooncol 113:65–74. doi:10.1007/s11060-013-1090-x
116. Nilsson RJA, Balaj L, Hulleman E, van Rijn S, Pegtel DM, Walraven M, Widmark A, Gerritsen WR, Verheul HM, Vandertop WP, Noske DP, Skog J, Würdinger T (2011) Blood platelets contain tumor-derived RNA biomarkers. Blood 118:3680–3683. doi:10.1182/blood-2011-03-344408
117. Noerholm M, Balaj L, Limperg T, Salehi A, Zhu LD, Hochberg FH, Breakefield XO, Carter BS, Skog J (2012) RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls. BMC Cancer 12:22. doi:10.1186/1471-2407-12-22
118. Olar A, Aldape KD (2014) Using the molecular classification of glioblastoma to inform personalized treatment. J Pathol 232:165–177. doi:10.1002/path.4282
119. Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J (2014) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol 16(Suppl 4):iv1–iv63. doi:10.1093/neuonc/nou223
120. Pantel K, Alix-Panabières C, Riethdorf S (2009) Cancer micrometastases. Nat Rev Clin Oncol 6:339–351. doi:10.1038/nrclinonc.2009.44
121. Parsons DW, Jones S, Zhang X, Lin JC-H, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu I-M, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812. doi:10.1126/science.1164382
122. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suva ML, Regev A, Bernstein BE (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344:1396–1401. doi:10.1126/science.1254257
123. Patrick Y, Wen SK (2008) Malignant gliomas in adults. N Engl J Med 359:1850. doi:10.1056/NEJMc086380 (author reply 1850)
124. Peles E, Lidar Z, Simon AJ, Grossman R, Nass D, Ram Z (2004) Angiogenic factors in the cerebrospinal fluid of patients with astrocytic brain tumors. Neurosurgery 55:562–568. doi:10.1227/01.NEU.0000134383.27713.9A
125. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157–173. doi:10.1016/j.ccr.2006.02.019
126. Preusser M (2014) Neuro-oncology: a step towards clinical blood biomarkers of glioblastoma. Nat Rev Neurol 10:681–682. doi:10.1038/nrneurol.2014.208
127. Quaranta M, Divella R, Daniele A, Di Tardo S, Venneri MT, Lolli I, Troccoli G (2007) Epidermal growth factor receptor serum levels and prognostic value in malignant gliomas. Tumori 93:275–280
128. Rafat N, Beck GC, Schulte J, Tuettenberg J, Vajkoczy P (2010) Circulating endothelial progenitor cells in malignant gliomas. J Neurosurg 112:43–49. doi:10.3171/2009.5.JNS081074
129. Restrepo L, Stafford P, Magee DM, Johnston SA (2011) Application of immunosignatures to the assessment of Alzheimer’s disease. Ann Neurol 70:286–295. doi:10.1002/ana.22405
130. Reynés G, Vila V, Fleitas T, Reganon E, Font de Mora J, Jordá M, Martínez-Sales V (2013) Circulating endothelial cells and procoagulant microparticles in patients with glioblastoma: prognostic value. PLoS One 8:e69034. doi:10.1371/journal.pone.0069034
131. Reynés G, Vila V, Martín M, Parada A, Fleitas T, Reganon E, Martínez-Sales V (2011) Circulating markers of angiogenesis, inflammation, and coagulation in patients with glioblastoma. J Neurooncol 102:35–41. doi:10.1007/s11060-010-0290-x
132. Rhodes CH, Honsinger C, Sorenson GD (1994) Detection of tumor-derived DNA in cerebrospinal fluid. J Neuropathol Exp Neurol 53:364–368
133. Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre J-Y (2012) Primary brain tumours in adults. Lancet 379:1984–1996. doi:10.1016/S0140-6736(11)61346-9
134. Risitano A, Beaulieu LM, Vitseva O, Freedman JE (2012) Platelets and platelet-like particles mediate intercellular RNA transfer. Blood 119:6288–6295. doi:10.1182/blood-2011-12-396440
135. Rohle D, Popovici-Muller J, Palaskas N, Turcan S, Grommes C, Campos C, Tsoi J, Clark O, Oldrini B, Komisopoulou E, Kunii K, Pedraza A, Schalm S, Silverman L, Miller A, Wang F, Yang H, Chen Y, Kernytsky A et al (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 340:626–630. doi:10.1126/science.1236062
136. Roth P, Wischhusen J, Happold C, Chandran PA, Hofer S, Eisele G, Weller M, Keller A (2011) A specific miRNA signature in the peripheral blood of glioblastoma patients. J Neurochem 118:449–457. doi:10.1111/j.1471-4159.2011.07307.x
137. Roux-Lombard P, Pagano S, Montecucco F, Satta N, Vuilleumier N (2013) Auto-antibodies as emergent prognostic markers and possible mediators of ischemic cardiovascular diseases. Clin Rev Allergy Immunol 44:84–97. doi:10.1007/s12016-010-8233-z
138. Roy R, Yang J, Moses MA (2009) Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 27:5287–5297. doi:10.1200/JCO.2009.23.5556
139. Nishikawa R, Saran F, Mason W, Wick W, Cloughesy TF, Henriksson R, Hilton M, Garcia J, Vogt T, Pallaud C, Chinot OL (2013) Biomarker (BM) evaluations in the phase III AVAglio study of bevacizumab (Bv) plus standard radiotherapy (RT) and temozolomide (T) for newly diagnosed glioblastoma (GBM). J Clin Oncol 31 (suppl; abstr 2023^)
140. Salkeni MA, Zarzour A, Ansay TY, McPherson CM, Warnick RE, Rixe O, Bahassi EM (2013) Detection of EGFRvIII mutant DNA in the peripheral blood of brain tumor patients. J Neurooncol 115:27–35. doi:10.1007/s11060-013-1209-0
141. Salmaggi A, Eoli M, Frigerio S, Ciusani E, Silvani A, Boiardi A (1999) Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and plasma thrombomodulin levels in glioblastoma patients. Cancer Lett 146:169–172
142. Sampath P, Weaver CE, Sungarian A, Cortez S, Alderson L, Stopa EG (2004) Cerebrospinal fluid (vascular endothelial growth factor) and serologic (recoverin) tumor markers for malignant glioma. Cancer Control 11:174–180
143. Saratsis AM, Yadavilli S, Magge S, Rood BR, Perez J, Hill DA, Hwang E, Kilburn L, Packer RJ, Nazarian J (2012) Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid. Neuro Oncol 14:547–560. doi:10.1093/neuonc/nos067
144. Sato Y, Honda Y, Asoh T, Oizumi K, Ohshima Y, Honda E (1998) Cerebrospinal fluid ferritin in glioblastoma: evidence for tumor synthesis. J Neurooncol 40:47–50
145. Sawaya R, Cummins C, Smith B, Kornblith P (1985) Plasma fibronectin in patients with brain tumors. Neurosurgery. 16:161–165
146. Schmidt C (2011) Larger companies dominate cancer companion diagnostic approvals. Nat Biotechnol 29:955–957. doi:10.1038/nbt1111-955
147. Schneider T, Sailer M, Ansorge S, Firsching R, Reinhold D (2006) Increased concentrations of transforming growth factor beta1 and beta2 in the plasma of patients with glioblastoma. J Neurooncol 79:61–65. doi:10.1007/s11060-005-9116-7
148. Schuhmann MU, Zucht HD, Nassimi R, Heine G, Schneekloth CG, Stuerenburg HJ, Selle H (2010) Peptide screening of cerebrospinal fluid in patients with glioblastoma multiforme. Eur J Surg Oncol 36:201–207. doi:10.1016/j.ejso.2009.07.010
149. Schwarzenbach H, Hoon DSB, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11:426–437. doi:10.1038/nrc3066
150. Schwarzenbach H, Nishida N, Calin GA, Pantel K (2014) Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol 11:145–156. doi:10.1038/nrclinonc.2014.5
151. Shao H, Chung J, Balaj L, Charest A, Bigner DD, Carter BS, Hochberg FH, Breakefield XO, Weissleder R, Lee H (2012) Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat Med 18:1835–1840. doi:10.1038/nm.2994
152. Shao N, Wang L, Xue L, Wang R, Lan Q (2014) Plasma miR-454-3p as a potential prognostic indicator in human glioma. Neurol Sci. doi:10.1007/s10072-014-1938-7
153. Shnaper S, Desbaillets I, Brown DA, Murat A, Migliavacca E, Schluep M, Ostermann S, Hamou M-F, Stupp R, Breit SN, de Tribolet N, Hegi ME (2009) Elevated levels of MIC-1/GDF15 in the cerebrospinal fluid of patients are associated with glioblastoma and worse outcome. Int J Cancer 125:2624–2630. doi:10.1002/ijc.24639
154. Siebzehnrubl FA, Reynolds BA, Vescovi A, Steindler DA, Deleyrolle LP (2011) The origins of glioma: E Pluribus Unum? Glia 59:1135–1147. doi:10.1002/glia.21143
155. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476. doi:10.1038/ncb1800
156. Sottoriva A, Spiteri I, Piccirillo SGM, Touloumis A, Collins VP, Marioni JC, Curtis C, Watts C, Tavaré S (2013) Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci 110:4009–4014. doi:10.1073/pnas.1219747110
157. Sreekanthreddy P, Srinivasan H, Kumar DM, Nijaguna MB, Sridevi S, Vrinda M, Arivazhagan A, Balasubramaniam A, Hegde AS, Chandramouli BA, Santosh V, Rao MRS, Kondaiah V, Somasundaram K (2010) Identification of potential serum biomarkers of glioblastoma: serum osteopontin levels correlate with poor prognosis. Cancer Epidemiol Biomarkers Prev 19:1409–1422. doi:10.1158/1055-9965.EPI-09-1077
158. Strojnik T, Smigoc T, Lah TT (2014) Prognostic value of erythrocyte sedimentation rate and C-reactive protein in the blood of patients with glioma. Anticancer Res 34:339–347
159. Stupp R, Tonn J-C, Brada M, Pentheroudakis G (2010) High-grade malignant glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21(Suppl 5):v190–v193. doi:10.1093/annonc/mdq187
160. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, 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 352:987–996. doi:10.1056/NEJMoa043330
161. Sturm D, Witt H, Hovestadt V, Khuong-Quang D-A, Jones DTW, Konermann C, Pfaff E, Tönjes M, Sill M, Bender S, Kool M, Zapatka M, Becker N, Zucknick M, Hielscher T, Liu X-Y, Fontebasso AM, Ryzhova M, Albrecht S et al (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:425–437. doi:10.1016/j.ccr.2012.08.024
162. Sullivan JP, Nahed BV, Madden MW, Oliveira SM, Springer S, Bhere D, Chi AS, Wakimoto H, Rothenberg SM, Sequist LV, Kapur R, Shah K, Iafrate AJ, Curry WT, Loeffler JS, Batchelor TT, Louis DN, Toner M, Maheswaran S et al (2014) Brain tumor cells in circulation are enriched for mesenchymal gene expression. Cancer Discov. doi:10.1158/2159-8290.CD-14-0471
163. Taal W, Brandsma D, de Bruin HG, Bromberg JE, Swaak-Kragten AT, Smitt PA, van Es CA, van den Bent MJ (2008) Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer 113:405–410. doi:10.1002/cncr.23562
164. Tabatabai G, Stupp R, van den Bent MJ, Hegi ME, Tonn JC, Wick W, Weller M (2010) Molecular diagnostics of gliomas: the clinical perspective. Acta Neuropathol 120:585–592. doi:10.1007/s00401-010-0750-6
165. Tabouret E, Boudouresque F, Barrie M, Matta M, Boucard C, Loundou A, Carpentier A, Sanson M, Metellus P, Figarella-Branger D, Ouafik L, Chinot O (2014) Association of matrix metalloproteinase 2 plasma level with response and survival in patients treated with bevacizumab for recurrent high-grade glioma. Neuro Oncol 16:392–399. doi:10.1093/neuonc/not226
166. Tanaka S, Louis DN, Curry WT, Batchelor TT, Dietrich J (2013) Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end? Nat Rev Clin Oncol 10:14–26. doi:10.1038/nrclinonc.2012.204
167. Tanwar MK, Gilbert MR, Holland EC (2002) Gene expression microarray analysis reveals YKL-40 to be a potential serum marker for malignant character in human glioma. Cancer Res 62:4364–4368
168. Tektonidou MG, Ward MM (2011) Validation of new biomarkers in systemic autoimmune diseases. Nat Rev Rheumatol 7:708–717. doi:10.1038/nrrheum.2011.157
169. The Cancer Genome Atlas research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068. doi:10.1038/nature07385
170. Van Thuijl HF, Ylstra B, Würdinger T, van Nieuwenhuizen D, Heimans JJ, Wesseling P, Reijneveld JC (2013) Genetics and pharmacogenomics of diffuse gliomas. Pharmacol Ther 137:78–88. doi:10.1016/j.pharmthera.2012.09.002
171. Todaro L, Christiansen S, Varela M, Campodónico P, Pallotta MG, Lastiri J, Sacerdote de Lustig E, de Kier Bal, Joffé E, Puricelli L (2007) Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in patients with brain tumors. J Neurooncol 83:135–144. doi:10.1007/s11060-006-9312-0
172. Tykocinski ES, Grant RA, Kapoor GS, Krejza J, Bohman L-E, Gocke TA, Chawla S, Halpern CH, Lopinto J, Melhem ER, O’Rourke DM (2012) Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma. Neuro Oncol 14:613–623. doi:10.1093/neuonc/nos073
173. Unger EF, Goncalves L, Epstein SE, Chew EY, Trapnell CB, Cannon RO, Quyyumi AA (2000) Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris. Am J Cardiol 85:1414–1419
174. Verhaak RGW, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110. doi:10.1016/j.ccr.2009.12.020
175. Vos MJ, Postma TJ, Martens F, Uitdehaag BMJ, Blankenstein MA, Vandertop WP, Slotman BJ, Heimans JJ (2004) Serum levels of S-100B protein and neuron-specific enolase in glioma patients: a pilot study. Anticancer Res 24:2511–2514
176. Wakabayashi T, Natsume A, Hatano H, Fujii M, Shimato S, Ito M, Ohno M, Ito S, Ogura M, Yoshida J (2009) P16 promoter methylation in the serum as a basis for the molecular diagnosis of gliomas. Neurosurgery 64:455–461. doi:10.1227/01.NEU.0000340683.19920.E3 (discussion 461–462)
177. Wang LG, Setlow RB (1989) Inactivation of O6-alkylguanine-DNA alkyltransferase in HeLa cells by cisplatin. Carcinogenesis 10:1681–1684
178. Wang Q, Li P, Li A, Jiang W, Wang H, Wang J, Xie K (2012) Plasma specific miRNAs as predictive biomarkers for diagnosis and prognosis of glioma. J Exp Clin Cancer Res 31:97. doi:10.1186/1756-9966-31-97
179. Weller M, Felsberg J, Hartmann C, Berger H, Steinbach JP, Schramm J, Westphal M, Schackert G, Simon M, Tonn JC, Heese O, Krex D, Nikkhah G, Pietsch T, Wiestler O, Reifenberger G, von Deimling A, Loeffler M (2009) Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol 27:5743–5750. doi:10.1200/JCO.2009.23.0805
180. Weller M, Stupp R, Hegi ME, van den Bent M, Tonn JC, Sanson M, Wick W, Reifenberger G (2012) Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice. Neuro Oncol 14(Suppl 4):iv100–iv108. doi:10.1093/neuonc/nos206
181. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972. doi:10.1200/JCO.2009.26.3541
182. Wesseling P, Kros JM, Jeuken JWM (2011) The pathological diagnosis of diffuse gliomas: towards a smart synthesis of microscopic and molecular information in a multidisciplinary context. Diagn Histopathol 17:486–494. doi:10.1016/j.mpdhp.2011.08.005
183. Wick W, Weller M, van den Bent M, Sanson M, Weiler M, von Deimling A, Plass C, Hegi M, Platten M, Reifenberger G (2014) MGMT testing-the challenges for biomarker-based glioma treatment. Nat Rev Neurol 10:372–385. doi:10.1038/nrneurol.2014.100
184. Wiencke J, Accomando W, Zheng S (2012) Epigenetic biomarkers of T-cells in human glioma. Epigenetics. 7:1391–1402
185. Wood SL, Knowles MA, Thompson D, Selby PJ, Banks RE (2013) Proteomic studies of urinary biomarkers for prostate, bladder and kidney cancers. Nat Rev Urol 10:206–218. doi:10.1038/nrurol.2013.24
186. Wu W, Lamborn KR, Buckner JC, Novotny PJ, Chang SM, O’Fallon JR, Jaeckle KA, Prados MD (2010) Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma. Neuro Oncol 12:164–172. doi:10.1093/neuonc/nop019
187. Wurdinger T, Deumelandt K, van der Vliet HJ, Wesseling P, de Gruijl TD (2014) Mechanisms of intimate and long-distance cross-talk between glioma and myeloid cells: how to break a vicious cycle. Biochim Biophys Acta Rev Cancer 1846:560–575. doi:10.1016/j.bbcan.2014.10.003
188. Xu BJ, An QA, Srinivasa Gowda S, Yan W, Pierce LA, Abel TW, Rush SZ, Cooper MK, Ye F, Shyr Y, Weaver KD, Thompson RC (2012) Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma. Int J Oncol 40:1995–2003. doi:10.3892/ijo.2012.1355
189. Yamaguchi Y, Shao Z, Sharif S, Du X-Y, Myles T, Merchant M, Harsh G, Glantz M, Recht L, Morser J, Leung LLK (2013) Thrombin-cleaved fragments of osteopontin are overexpressed in malignant glial tumors and provide a molecular niche with survival advantage. J Biol Chem 288:3097–3111. doi:10.1074/jbc.M112.362954
190. Yang C, Wang C, Chen X, Chen S, Zhang Y, Zhi F, Wang J, Li L, Zhou X, Li N, Pan H, Zhang J, Zen K, Zhang C-Y, Zhang C (2013) Identification of seven serum microRNAs from a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas. Int J Cancer 132:116–127. doi:10.1002/ijc.27657
191. Yoshida J, Wakabayashi T (1994) Tenascin in cerebrospinal fluid is a useful biomarker for the diagnosis of brain tumour. J Neurol Neurosurg Psychiatry 57:1212–1215
192. Yoshida S, Morii K (2000) Serum concentrations of soluble interleukin-2 receptor in patients with malignant brain tumors. J Surg Oncol 75:131–135
193. Zheng P-P, Hop WC, Luider TM, Sillevis Smitt PA, Kros JM (2007) Increased levels of circulating endothelial progenitor cells and circulating endothelial nitric oxide synthase in patients with gliomas. Ann Neurol 62:40–48. doi:10.1002/ana.21151
194. Zheng P-P, Luider TM, Pieters R, Avezaat CJJ, van den Bent MJ, Sillevis Smitt PA, Kros JM (2003) Identification of tumor-related proteins by proteomic analysis of cerebrospinal fluid from patients with primary brain tumors. J Neuropathol Exp Neurol 62:855–862
195. Zucker S, Cao J (2005) Measurement of matrix metalloproteinases in serum of patients with melanoma: snarled in technical pitfalls. Clin Cancer Res 11:5069–5070. doi:10.1158/1078-0432.CCR-05-0774