Expression of Cancer/Testis Antigens is Correlated with Improved Survival in Glioblastoma
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Marcelo Roberto Pereira Freitas1, Suzana Maria Fleury Malheiros2, João Norberto Stávale3, Thais Priscila Biassi1, Fernando Tadeu Zamunér1, Maria Dirlei Ferreira de Souza Begnami4, Fernando Augusto Soares4, Andre Luíz Vettore1
1 Cancer Molecular Biology Laboratory, Department of Science Biology, Federal University of São Paulo, Rua Pedro de Toledo, São Paulo, SP, Brazil
2 Department of Neurology, Federal University of São Paulo, Rua Botucatú,São Paulo, SP – Brazil
3 Department of Pathology, Federal University of São Paulo, Rua Botucatú, São Paulo, SP – Brazil
4 Department of Pathology, A C Camargo Cancer Hospital, Rua Prof. Antônio Prudente, São Paulo, SP, Brazil.
André L. Vettore, email:
Keywords: Brain cancer, Glioblastoma, GBM, Cancer/Testis antigens, CTA expression
Received: March 27, 2013 Accepted: April 13, 2013 Published: April 15, 2013
Background: Glioblastoma (GBM) confers a dismal prognosis despite advances in current therapy. Cancer-testis antigens (CTA) comprise families of tumor-associated antigens that are immunogenic in different cancers. The aim of this study was to determine the expression profile of a large number of CTA genes in GBM.
Methods: We selected, from 153 CTA genes, those genes potentially expressed in GBM. The expression pattern of 30 CTA was then evaluated by RT-PCR in a series of 48 GBM and 5 normal brain samples. The presence of CTCFL protein was also evaluated by immunohistochemical staining.
Results: Among the genes with no expression in normal brain, ACTL8 (57%), OIP5 (54%), XAGE3 (44%) and CTCFL (15%) were frequently expressed in GBM, while over 85% of the tumors expressed at least 1 of these four CTA. Coexpression of two or more CTA occurred in 49% of cases. CTCFL protein expression was detected in 13% of the GBM and was negative in normal brain samples. GBM expressing 3-4 CTA was associated with significantly better overall survival (OS) rates (P = 0.017). By multivariate analysis, mRNA positivity for 3-4 CTA (P = 0.044), radiotherapy (P = 0.010) and chemotherapy (P = 0.001) were independent prognostic factors for OS.
Conclusions: GBM frequently express ACTL8, OIP5, XAGE3 and CTCFL. A relatively high percentage of tumors expressed at least one of these four CTA, opening the perspective for their utility in antigen-specific immunotherapy. Furthermore, mRNA positivity for 3-4 CTA is an independent predictor of better OS for GBM patients.
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