Oncotarget

Research Papers:

Expression of Cancer/Testis Antigens is Correlated with Improved Survival in Glioblastoma

Marcelo R.P. Freitas, Suzana M.F. Malheiros, João N. Stávale, Thaís P. Biassi, Fernando T. Zamunér, Maria D.F.S. Begnami, Fernado A. Soares and André L. Vettore _

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Oncotarget. 2013; 4:636-646. https://doi.org/10.18632/oncotarget.950

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Abstract

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.

Correspondence:

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

Abstract

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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