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

// Marcelo Roberto Pereira Freitas 1 , Suzana Maria Fleury Malheiros 2 , Joao Norberto Stavale 3 , Thais Priscila Biassi 1 , Fernando Tadeu Zamuner 1 , Maria Dirlei Ferreira de Souza Begnami 4 , Fernando Augusto Soares 4 , Andre Luiz Vettore 1 1 Cancer Molecular Biology Laboratory, Department of Science Biology, Federal University of Sao Paulo, Rua Pedro de Toledo, Sao Paulo, SP, Brazil 2 Department of Neurology, Federal University of Sao Paulo, Rua Botucatu,Sao Paulo, SP – Brazil 3 Department of Pathology, Federal University of Sao Paulo, Rua Botucatu, Sao Paulo, SP – Brazil 4 Department of Pathology, A C Camargo Cancer Hospital, Rua Prof. Antonio Prudente, Sao Paulo, SP, Brazil. Correspondence: Andre 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.