title: Robustness of equations that define molecular subtypes of glioblastoma tumors based on five transcripts measured by RT-PCR.
abstract: Glioblastoma (Gb) is one of the most deadly tumors. Its molecular subtypes are yet to be fully characterized while the attendant efforts for personalized medicine need to be intensified in relation to glioblastoma diagnosis, treatment, and prognosis. Several molecular signatures based on gene expression microarrays were reported, but the use of microarrays for routine clinical practice is challenged by attendant economic costs. Several authors have proposed discriminant equations based on RT-PCR. Still, the discriminant threshold is often incompletely described, which makes proper validation difficult. In a previous work, we have reported two Gb subtypes based on the expression levels of four genes: CHI3L1, LDHA, LGALS1, and IGFBP3. One Gb subtype presented with low expression of the four genes mentioned, and of MGMT in a large portion of the patients (with anticipated high methylation of its promoter), and mutated IDH1. Here, we evaluate the robustness of the equations fitted with these genes using RT-PCR values in a set of 64 cases and importantly, define an unequivocal discriminant threshold with a view to prognostic implications. We developed two approaches to generate the discriminant equations: 1) using the expression level of the four genes mentioned above, and 2) using those genes displaying the highest correlation with survival among the aforementioned four ones, plus MGMT, as an attempt to further reduce the number of genes. The ease of equations' applicability, reduction in cost for raw data, and robustness in terms of resampling-based classification accuracy warrant further evaluation of these equations to discern Gb tumor biopsy heterogeneity at molecular level, diagnose potential malignancy, and prognosis of individual patients with glioblastomas.
authors.affiliation: 1 Servei de Genòmica i Bioinformàtica, Universitat Autònoma de Barcelona , Cerdanyola del Vallès, Spain .
authors.forename: Xavier
authors.initials: X
authors.lastname: Castells
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Acebes
authors.forename: Carles
authors.initials: C
authors.lastname: Majós
authors.forename: Susana
authors.initials: S
authors.lastname: Boluda
authors.forename: Margarida
authors.initials: M
authors.lastname: Julià-Sapé
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Candiota
authors.forename: Joaquín
authors.initials: J
authors.lastname: Ariño
authors.forename: Anna
authors.initials: A
authors.lastname: Barceló
authors.forename: Carles
authors.initials: C
authors.lastname: Arús
mesh_terms: D054392:Adipokines / Q000235:genetics; D000071451:Chitinase-3-Like Protein 1; D037483:Galectin 1 / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D037102:Lectins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037483:Galectin 1; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D037102:Lectins