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Automated Brain Tumor Biopsy Prediction Using Single-labeling cDNA Microarrays-based Gene Expression Profiling

Castells, Xavier PhD* †; García-Gómez, Juan Miguel PhD; Navarro, Alfredo MSc; Acebes, Juan José PhD, MD† §; Godino, Óscar MD† §; Boluda, Susana MD; Barceló, Anna PhD† ¶; Robles, Montserrat PhD; Ariño, Joaquín PhD† ¶; Arús, Carles PhD* †

Diagnostic Molecular Pathology: December 2009 - Volume 18 - Issue 4 - pp 206-218
doi: 10.1097/PDM.0b013e31818f071b
Original Articles
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Aims: Gene signatures obtained from microarray experiments may be of use to improve the prediction of brain tumor diagnosis. Nevertheless, automated and objective prediction with accuracy comparable to or better than the gold standard should be convincingly demonstrated for possible clinician uptake of the new methodology. Herewith, we demonstrate that primary brain tumor types can be discriminated using microarray data in an automated and objective way.

Methods: Postsurgical biopsies from 35 patients [17 glioblastoma multiforme (Gbm) and 18 meningothelial meningioma (Mm)] were stored in liquid nitrogen, total RNA was extracted, and cDNA was labeled with Cy3 fluorochrome and hybridized onto a cDNA-based microarray containing 11,500 cDNA clones representing 9300 loci. Scanned data were preprocessed, normalized, and used for predictor development. The predictive functions were fitted to a subset of samples and their performance evaluated with an independent subset. Expression results were validated by means of real time-polymerase chain reaction.

Results: Some gene expression-based predictors achieved 100% accuracy both in training resampling validation and independent testing. One of them, composed of GFAP, PTPRZ1, GPM6B and PRELP, produced a 100% prediction accuracy for both training and independent test datasets. Furthermore, the gene signatures obtained, increased cell detoxification, motility and intracellular transport in Gbm, and increased cell adhesion and cytochrome-family genes in Mm, agree well with the expected biologic and pathologic characteristics of the studied tumors.

Conclusions: The ability of gene signatures to automate prediction of brain tumors through a fully objective approach has been demonstrated. A comparison of gene expression profiles between Gbm and Mm may provide additional clues about patterns associated with each tumor type.

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*Grup d'aplicacions Biomèdiques de la RMN (GABRMN), Departament de Bioquímica i Biologia Molecular, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès

Informàtica Biomèdica-BET, Universitat Politècnica de València, València

§Departament de Neurocirurgia, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat

Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat

Departament de Bioquímica i Biologia Molecular, Facultat de Veterinària, Universitat Autònoma de Barcelona, Cerdanyola del Vallès

Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès

Xavier Castells, PhD and Juan Miguel García-Gómez, PhD, have equally contributed to this work.

Supported in part by grants from the European Commission (FP6-2002-LIFESCIHEALTH 503094 and IST-2004-27214), the research project MEDIVO2 (MEC, SAF2005-03650), and the Programa de Apoyo a la Investigación y Desarrollo (PAID-00-06 UPV).

Reprints: Prof Carles Arús, PhD, Facultat de Biociències, Cerdanyola del Vallès, Universitat Autònoma de Barcelona, Barcelona, Spain 08193 (e-mail: carles.arus@uab.cat).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journals Web site (http://www.molecularpathology.com).

© 2009 Lippincott Williams & Wilkins, Inc.