TY - JOUR
T1 - Using urinary bFGF and TIMP3 levels to predict the presence of juvenile pilocytic astrocytoma and establish a distinct biomarker signature
AU - Fehnel, Katie Pricola
AU - Duggins-Warf, Micah
AU - Zurakowski, David
AU - McKee-Proctor, Maxwell
AU - Majumder, Rajarshi
AU - Raber, Michael
AU - Han, Xuezhe
AU - Smith, Edward R.
N1 - Funding Information:
Acknowledgments We would like to thank Kristen Johnson for preparation of the article and Marsha Moses, PhD, for her review of this manuscript and for all of her research support. This study was funded by Voices Against Brain Cancer and the Christopher Fellows Brain Tumor Research Fund (Dr. Smith), and the Neurosurgery Research and Education Foundation and AANS/CNS Section of Pediatric Neurological Surgery Research Fellowship (Dr. Pricola Fehnel).
Publisher Copyright:
© AANS, 2016.
PY - 2016/10
Y1 - 2016/10
N2 - Objective The authors report the use of urinary biomarkers as a novel, noninvasive technique to detect juvenile pilocytic astrocytomas (JPAs), capable of distinguishing JPAs from other CNS diseases, including other brain tumors. Preliminary screening of an array of tumors implicated proteases (including matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinase [TIMPs]) as well as growth factors (including basic fibroblast growth factor [bFGF]) as candidate biomarkers. These data led the authors to hypothesize that tissue inhibitor of metalloproteinase 3 (TIMP3) and bFGF would represent high-probability candidates as JPA-specific biomarkers. Methods Urine was collected from 107 patients, which included children with JPA (n = 21), medulloblastoma (n = 17), glioblastoma (n = 9), arteriovenous malformations (n = 25), moyamoya (n = 14), and age-and sex-matched controls (n = 21). Biomarker levels were quantified with enzyme-linked immunosorbent assay, tumor tissue expression was confirmed with immunohistochemical analysis, and longitudinal biomarker expression was correlated with imaging. Results were subjected to univariate and multivariate statistical analyses. Results Using optimal urinary cutoff values of bFGF > 1.0 pg/g and TIMP3 > 3.5 pg/g, multiplexing bFGF and TIMP3 predicts JPA presence with 98% accuracy. Multiplexing bFGF and MMP13 distinguishes JPA from other brain tumor subtypes with up to 98% accuracy. Urinary biomarker expression correlated with both tumor immunohistochemistry and in vitro tumor levels. Urinary bFGF and TIMP3 decrease following successful tumor treatment and correlate with changes in tumor size. Conclusions This study identifies 2 urinary biomarkers-bFGF and TIMP3-that successfully detect one of the most common pediatric brain tumors with high accuracy. These data highlight potential benefits of urinary biomarkers and support their utility as diagnostic tools in the treatment of children with JPA.
AB - Objective The authors report the use of urinary biomarkers as a novel, noninvasive technique to detect juvenile pilocytic astrocytomas (JPAs), capable of distinguishing JPAs from other CNS diseases, including other brain tumors. Preliminary screening of an array of tumors implicated proteases (including matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinase [TIMPs]) as well as growth factors (including basic fibroblast growth factor [bFGF]) as candidate biomarkers. These data led the authors to hypothesize that tissue inhibitor of metalloproteinase 3 (TIMP3) and bFGF would represent high-probability candidates as JPA-specific biomarkers. Methods Urine was collected from 107 patients, which included children with JPA (n = 21), medulloblastoma (n = 17), glioblastoma (n = 9), arteriovenous malformations (n = 25), moyamoya (n = 14), and age-and sex-matched controls (n = 21). Biomarker levels were quantified with enzyme-linked immunosorbent assay, tumor tissue expression was confirmed with immunohistochemical analysis, and longitudinal biomarker expression was correlated with imaging. Results were subjected to univariate and multivariate statistical analyses. Results Using optimal urinary cutoff values of bFGF > 1.0 pg/g and TIMP3 > 3.5 pg/g, multiplexing bFGF and TIMP3 predicts JPA presence with 98% accuracy. Multiplexing bFGF and MMP13 distinguishes JPA from other brain tumor subtypes with up to 98% accuracy. Urinary biomarker expression correlated with both tumor immunohistochemistry and in vitro tumor levels. Urinary bFGF and TIMP3 decrease following successful tumor treatment and correlate with changes in tumor size. Conclusions This study identifies 2 urinary biomarkers-bFGF and TIMP3-that successfully detect one of the most common pediatric brain tumors with high accuracy. These data highlight potential benefits of urinary biomarkers and support their utility as diagnostic tools in the treatment of children with JPA.
KW - BFGF
KW - Basic fibroblast growth factor
KW - Oncology
KW - Pilocytic astrocytoma
KW - TIMP3
KW - Tissue inhibitor of metalloproteinase 3
KW - Urinary biomarkers
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U2 - 10.3171/2015.12.PEDS15448
DO - 10.3171/2015.12.PEDS15448
M3 - Article
C2 - 27314542
AN - SCOPUS:84990853638
SN - 1933-0707
VL - 18
SP - 396
EP - 407
JO - Journal of Neurosurgery: Pediatrics
JF - Journal of Neurosurgery: Pediatrics
IS - 4
ER -