Using urinary bFGF and TIMP3 levels to predict the presence of juvenile pilocytic astrocytoma and establish a distinct biomarker signature
| Autor: | Rajarshi Majumder, David Zurakowski, Maxwell McKee-Proctor, Micah Duggins-Warf, Katie Pricola Fehnel, Xuezhe Han, Michael Raber, Edward R. Smith |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Pathology medicine.medical_specialty Urinary system Basic fibroblast growth factor Brain tumor Fluorescent Antibody Technique Enzyme-Linked Immunosorbent Assay Astrocytoma Arteriovenous Malformations 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Matrix Metalloproteinase 13 Biomarkers Tumor medicine Humans Longitudinal Studies Child Tissue Inhibitor of Metalloproteinase-3 Medulloblastoma Pilocytic astrocytoma Brain Neoplasms business.industry Juvenile Pilocytic Astrocytoma General Medicine Tissue inhibitor of metalloproteinase medicine.disease chemistry 030220 oncology & carcinogenesis Multivariate Analysis Biomarker (medicine) Female Fibroblast Growth Factor 2 Moyamoya Disease business 030217 neurology & neurosurgery Follow-Up Studies |
| Zdroj: | Journal of Neurosurgery: Pediatrics. 18:396-407 |
| ISSN: | 1933-0715 1933-0707 |
| DOI: | 10.3171/2015.12.peds15448 |
| Popis: | 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/μg and TIMP3 > 3.5 pg/μg, 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. |
| Databáze: | OpenAIRE |
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