Freitas Marcelo, Malheiros Suzana, Stávale João Norberto, Biassi Thais Priscila, Zamunér Fernando Tadeu, de Souza Begnami Maria, Soares Fernando Augusto, Vettore Andre Luíz
Cancer Molecular Biology Laboratory, Department of Science Biology, Federal University of São Paulo, Rua Pedro de Toledo, São Paulo, SP, Brazil.
Oncotarget. 2013 Apr;4(4):636-46. doi: 10.18632/oncotarget.950.
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.
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.
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.
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.
尽管当前治疗取得了进展，但胶质母细胞瘤（GBM）的预后仍然很差。癌-睾丸抗原（CTA）由在不同癌症中具有免疫原性的肿瘤相关抗原家族组成。本研究的目的是确定大量CTA基因在GBM中的表达谱。
我们从153个CTA基因中筛选出可能在GBM中表达的基因。然后通过逆转录聚合酶链反应（RT-PCR）在48例GBM和5例正常脑样本中评估30个CTA的表达模式。还通过免疫组织化学染色评估了CTCFL蛋白的存在情况。
在正常脑中无表达的基因中，ACTL8（57%）、OIP5（54%）、XAGE3（44%）和CTCFL（15%）在GBM中频繁表达，而超过85%的肿瘤表达这四种CTA中的至少一种。49%的病例中出现两种或更多CTA的共表达。在13%的GBM中检测到CTCFL蛋白表达，在正常脑样本中为阴性。表达3 - 4种CTA的GBM与显著更好的总生存率（OS）相关（P = 0.017）。通过多变量分析，3 - 4种CTA的mRNA阳性（P = 0.044）、放疗（P = 0.010）和化疗（P = 0.001）是OS的独立预后因素。
GBM频繁表达ACTL8、OIP5、XAGE3和CTCFL。相对较高比例的肿瘤表达这四种CTA中的至少一种，为它们在抗原特异性免疫治疗中的应用开辟了前景。此外，3 - 4种CTA的mRNA阳性是GBM患者OS更好的独立预测指标。
