title: Combined epidermal growth factor receptor and Beclin1 autophagic protein expression analysis identifies different clinical presentations, responses to chemo- and radiotherapy, and prognosis in glioblastoma.
abstract: Dysregulated EGFR in glioblastoma may inactivate the key autophagy protein Beclin1. Each of high EGFR and low Beclin1 protein expression, independently, has been associated with tumor progression and poor prognosis. High (H) compared to low (L) expression of EGFR and Beclin1 is here correlated with main clinical data in 117 patients after chemo- and radiotherapy. H-EGFR correlated with low Karnofsky performance and worse neurological performance status, higher incidence of synchronous multifocality, poor radiological evidence of response, shorter progression disease-free (PDFS), and overall survival (OS). H-Beclin1 cases showed better Karnofsky performance status, higher incidence of objective response, longer PDFS, and OS. A mutual strengthening effect emerges in correlative power of stratified L-EGFR and H-Beclin1 expression with incidence of radiological response after treatment, unifocal disease, and better prognosis, thus identifying an even longer OS group (30 months median OS compared to 18 months in L-EGFR, 15 months in H-Beclin1, and 11 months in all GBs) (P = 0.0001). Combined L-EGFR + H-Beclin1 expression may represent a biomarker in identifying relatively favorable clinical presentations and prognosis, thus envisaging possible EGFR/Beclin1-targeted therapies.
authors.affiliation: Tuscan Tumor Institute (ITT), 50139 Florence, Italy ; Unit of Radiation Oncology, University Hospital of Siena, 53100 Siena, Italy ; Department of Medicine, Surgery and Neurological Sciences, Research Center for Molecular Radiobiology, University of Siena, 53100 Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tini
authors.affiliation: Tuscan Tumor Institute (ITT), 50139 Florence, Italy ; Department of Medicine, Surgery and Neurological Sciences, Research Center for Molecular Radiobiology, University of Siena, 53100 Siena, Italy ; Unit of Pathological Anatomy, Department of Medicine, Surgery and Neurological Sciences, University of Siena, 53100 Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Belmonte
authors.affiliation: Tuscan Tumor Institute (ITT), 50139 Florence, Italy ; Department of Medicine, Surgery and Neurological Sciences, Research Center for Molecular Radiobiology, University of Siena, 53100 Siena, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Toscano
authors.affiliation: Tuscan Tumor Institute (ITT), 50139 Florence, Italy ; Department of Medicine, Surgery and Neurological Sciences, Research Center for Molecular Radiobiology, University of Siena, 53100 Siena, Italy ; Unit of Pathological Anatomy, Department of Medicine, Surgery and Neurological Sciences, University of Siena, 53100 Siena, Italy.
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Palumbo
authors.affiliation: Tuscan Tumor Institute (ITT), 50139 Florence, Italy ; Department of Medicine, Surgery and Neurological Sciences, Research Center for Molecular Radiobiology, University of Siena, 53100 Siena, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Pastina
authors.affiliation: Tuscan Tumor Institute (ITT), 50139 Florence, Italy ; Department of Medicine, Surgery and Neurological Sciences, Research Center for Molecular Radiobiology, University of Siena, 53100 Siena, Italy.
authors.forename: Giuseppe
authors.identifier: 0000-0003-3941-5302
authors.initials: G
authors.lastname: Battaglia
authors.affiliation: Tuscan Tumor Institute (ITT), 50139 Florence, Italy ; Department of Medicine, Surgery and Neurological Sciences, Research Center for Molecular Radiobiology, University of Siena, 53100 Siena, Italy.
authors.forename: Valerio
authors.identifier: 0000-0002-7347-0965
authors.initials: V
authors.lastname: Nardone
authors.affiliation: Department of Medicine, Surgery and Neurological Sciences, Research Center for Molecular Radiobiology, University of Siena, 53100 Siena, Italy ; Unit of Pathological Anatomy, Department of Medicine, Surgery and Neurological Sciences, University of Siena, 53100 Siena, Italy.
authors.forename: Marie Aimée Gloria Munezero
authors.initials: MA
authors.lastname: Butorano
authors.affiliation: Unit of Preventive Medicine, Moscati Hospital, 83100 Avellino, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Masucci
authors.affiliation: Unit of Neuroradiology, University Hospital of Siena, 53100 Siena, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cerase
authors.affiliation: Tuscan Tumor Institute (ITT), 50139 Florence, Italy ; Unit of Radiation Oncology, University Hospital of Siena, 53100 Siena, Italy ; Department of Medicine, Surgery and Neurological Sciences, Research Center for Molecular Radiobiology, University of Siena, 53100 Siena, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Pirtoli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D000071186:Beclin-1; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D059248:Chemoradiotherapy; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D008565:Membrane Proteins; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors
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