Proteins inform survival-based differences in patients with glioblastoma.

glioblastoma mass spectrometry proteomics survival

Journal

Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003

Informations de publication

Date de publication:
Historique:
entrez: 10 7 2020
pubmed: 10 7 2020
medline: 10 7 2020
Statut: epublish

Résumé

Improving the care of patients with glioblastoma (GB) requires accurate and reliable predictors of patient prognosis. Unfortunately, while protein markers are an effective readout of cellular function, proteomics has been underutilized in GB prognostic marker discovery. For this study, GB patients were prospectively recruited and proteomics discovery using liquid chromatography-mass spectrometry analysis (LC-MS/MS) was performed for 27 patients including 13 short-term survivors (STS) (≤10 months) and 14 long-term survivors (LTS) (≥18 months). Proteomics discovery identified 11 941 peptides in 2495 unique proteins, with 469 proteins exhibiting significant dysregulation when comparing STS to LTS. We verified the differential abundance of 67 out of these 469 proteins in a small previously published independent dataset. Proteins involved in axon guidance were upregulated in STS compared to LTS, while those involved in p53 signaling were upregulated in LTS. We also assessed the correlation between LS MS/MS data with RNAseq data from the same discovery patients and found a low correlation between protein abundance and mRNA expression. Finally, using LC-MS/MS on a set of 18 samples from 6 patients, we quantified the intratumoral heterogeneity of more than 2256 proteins in the multisample dataset. These proteomic datasets and noted protein variations present a beneficial resource for better predicting patient outcome and investigating potential therapeutic targets.

Sections du résumé

BACKGROUND BACKGROUND
Improving the care of patients with glioblastoma (GB) requires accurate and reliable predictors of patient prognosis. Unfortunately, while protein markers are an effective readout of cellular function, proteomics has been underutilized in GB prognostic marker discovery.
METHODS METHODS
For this study, GB patients were prospectively recruited and proteomics discovery using liquid chromatography-mass spectrometry analysis (LC-MS/MS) was performed for 27 patients including 13 short-term survivors (STS) (≤10 months) and 14 long-term survivors (LTS) (≥18 months).
RESULTS RESULTS
Proteomics discovery identified 11 941 peptides in 2495 unique proteins, with 469 proteins exhibiting significant dysregulation when comparing STS to LTS. We verified the differential abundance of 67 out of these 469 proteins in a small previously published independent dataset. Proteins involved in axon guidance were upregulated in STS compared to LTS, while those involved in p53 signaling were upregulated in LTS. We also assessed the correlation between LS MS/MS data with RNAseq data from the same discovery patients and found a low correlation between protein abundance and mRNA expression. Finally, using LC-MS/MS on a set of 18 samples from 6 patients, we quantified the intratumoral heterogeneity of more than 2256 proteins in the multisample dataset.
CONCLUSIONS CONCLUSIONS
These proteomic datasets and noted protein variations present a beneficial resource for better predicting patient outcome and investigating potential therapeutic targets.

Identifiants

DOI: 10.1093/noajnl/vdaa039 PMID: 32642694 PMC: PMC7212893
pubmed: 32642694
doi: 10.1093/noajnl/vdaa039
pii: vdaa039
pmc: PMC7212893
doi:

Types de publication

Journal Article

Langues

eng

Pagination

vdaa039

Subventions

Organisme : NCI NIH HHS
ID : T32 CA094186
Pays : United States

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

Références

Brief Bioinform. 2018 Sep 28;19(5):971-981
pubmed: 28369175
J Proteomics. 2011 Nov 18;74(12):2723-33
pubmed: 21356337
Neuro Oncol. 2017 Nov 6;19(suppl_5):v1-v88
pubmed: 29117289
Cell. 2016 Jul 28;166(3):755-765
pubmed: 27372738
J Neurosurg. 2001 Aug;95(2):190-8
pubmed: 11780887
Cancer Res. 2004 Apr 1;64(7):2496-501
pubmed: 15059904
Neuro Oncol. 2008 Feb;10(1):45-51
pubmed: 18182627
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
Future Oncol. 2013 Nov;9(11):1773-93
pubmed: 24156336
Proteomics. 2013 Feb;13(3-4):493-503
pubmed: 23019139
J Proteome Res. 2009 Oct;8(10):4604-14
pubmed: 19673542
Leuk Res. 2011 Jul;35(7):879-84
pubmed: 21146216
Front Oncol. 2012 Feb 28;2:19
pubmed: 22649779
Oncotarget. 2016 Aug 23;7(34):54632-54649
pubmed: 27429043
EBioMedicine. 2016 Oct;12:72-85
pubmed: 27667176
Sci Rep. 2019 Jul 29;9(1):10986
pubmed: 31358880
Int J Oncol. 2005 Apr;26(4):993-8
pubmed: 15753994
Cancer Cell. 2010 Jan 19;17(1):98-110
pubmed: 20129251
Cancer Cell. 2010 May 18;17(5):510-22
pubmed: 20399149
Oncotarget. 2017 Sep 18;8(63):107334-107345
pubmed: 29291033
Nature. 2016 May 25;534(7605):55-62
pubmed: 27251275
PLoS Comput Biol. 2013;9(9):e1003237
pubmed: 24068912
Sci Rep. 2017 Jul 28;7(1):6790
pubmed: 28754915
OMICS. 2009 Dec;13(6):467-76
pubmed: 20001861
Neuro Oncol. 2017 Jun 1;19(6):833-844
pubmed: 27932423
J Biol Chem. 2012 Sep 21;287(39):32512-24
pubmed: 22859294
N Engl J Med. 2005 Mar 10;352(10):997-1003
pubmed: 15758010
Bioinformatics. 2009 Oct 1;25(19):2573-80
pubmed: 19602524
Int J Cancer. 2014 Oct 15;135(8):1822-31
pubmed: 24615357
Nat Rev Neurosci. 2014 Jul;15(7):455-65
pubmed: 24946761
J Neurosurg. 2013 Apr;118(4):846-53
pubmed: 23082878
World J Gastroenterol. 2013 Jun 28;19(24):3792-801
pubmed: 23840117
Cancer Sci. 2009 Dec;100(12):2235-41
pubmed: 19737147
J Virol. 2009 Sep;83(18):9283-95
pubmed: 19587052
Asian Pac J Trop Med. 2015 Nov;8(11):952-957
pubmed: 26614996
Mol Cell Proteomics. 2016 Jul;15(7):2356-65
pubmed: 27143410
Proteome Sci. 2011 Apr 06;9(1):16
pubmed: 21470419
Dis Markers. 2014;2014:308976
pubmed: 24591759
Mol Biosyst. 2009 Dec;5(12):1512-26
pubmed: 20023718
Cell. 2013 Oct 10;155(2):462-77
pubmed: 24120142
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
BMC Bioinformatics. 2012;13 Suppl 16:S5
pubmed: 23176322
Mol Cell Proteomics. 2019 Oct;18(10):2029-2043
pubmed: 31353322
J Neurooncol. 2009 Aug;94(1):31-9
pubmed: 19219580
J Proteome Res. 2008 Jun;7(6):2270-9
pubmed: 18412385
J Proteome Res. 2009 Jan;8(1):82-93
pubmed: 18998720
Cancer Cell. 2006 Mar;9(3):157-73
pubmed: 16530701
Mol Cell Proteomics. 2012 Aug;11(8):381-93
pubmed: 22511458
Nature. 2014 Sep 18;513(7518):382-7
pubmed: 25043054
Physiol Genomics. 2014 Jul 1;46(13):467-81
pubmed: 24803679
Clin Transl Oncol. 2012 Sep;14(9):634-40
pubmed: 22855149
Stat Appl Genet Mol Biol. 2004;3:Article3
pubmed: 16646809
N Engl J Med. 2009 Feb 19;360(8):765-73
pubmed: 19228619
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931

Auteurs

L C Stetson (LC)

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Quinn T Ostrom (QT)

Department of Medicine and Division of Hematology-Oncology, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, Texas, USA.

Daniela Schlatzer (D)

Center for Proteomics and Bioinformatics and Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Peter Liao (P)

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Karen Devine (K)

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Kristin Waite (K)

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Department of Population and Quantitative Health Sciences and Cleveland Center for Health Outcomes Research (CCHOR), Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Marta E Couce (ME)

Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.

Peggy L R Harris (PLR)

Brain Tumor and Neuro-Oncology Center & Center of Excellence, Translational Neuro-Oncology, Department of Neurosurgery, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.

Amber Kerstetter-Fogle (A)

Brain Tumor and Neuro-Oncology Center & Center of Excellence, Translational Neuro-Oncology, Department of Neurosurgery, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.

Michael E Berens (ME)

Translational Genomics Research Institute (TGen), Phoenix, Arizona, USA.

Andrew E Sloan (AE)

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Brain Tumor and Neuro-Oncology Center & Center of Excellence, Translational Neuro-Oncology, Department of Neurosurgery, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.

Mohammad M Islam (MM)

Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.

Vilashini Rajaratnam (V)

Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.

Shama P Mirza (SP)

Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.

Mark R Chance (MR)

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Center for Proteomics and Bioinformatics and Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Jill S Barnholtz-Sloan (JS)

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Department of Population and Quantitative Health Sciences and Cleveland Center for Health Outcomes Research (CCHOR), Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
ORCID: 0000-0001-6190-9304

Classifications MeSH