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癌症-睾丸基因表达在非小细胞肺癌切除患者中的预后意义

Prognostic significance of cancer-testis gene expression in resected non-small cell lung cancer patients.

作者信息

Melloni Giulio, Ferreri Andres J M, Russo Vincenzo, Gattinoni Luca, Arrigoni Gianluigi, Ceresoli Giovanni Luca, Zannini Piero, Traversari Catia

机构信息

Department of Thoracic Surgery, Scientific Institute H. San Raffaele, Italy.

出版信息

Oncol Rep. 2004 Jul;12(1):145-51.

Abstract

MAGE, BAGE and GAGE genes encode T cell-defined tumor-associated antigens (TAA), which are expressed by various human tumors and are silent in normal tissues. Because of their expression pattern these TAA have received attention as potential targets for active immunotherapy and as molecular tumor markers. Both of these features are potentially useful in improving treatment of non-small cell lung cancer (NSCLC). We analyzed the expression of some members of the MAGE, BAGE and GAGE gene families by reverse transcription polymerase chain reaction (RT-PCR) in a cohort of 46 NSCLC patients who underwent complete resection and were followed-up for a median period of 41 months. A substantial proportion (range, 25-41%) of NSCLC expressed MAGE-A1, -A2, -A3, GAGE-1, -2, -8 and MAGE-B2 genes. On the contrary, BAGE and MAGE-B1 were expressed less frequently (17% and 11%, respectively). Overall, 59% of NSCLC patients expressed at least one gene and therefore could be eligible for tumor-specific immunotherapy protocols. Moreover, while MAGE-A, BAGE and MAGE-B genes did not provide any prognostic information, GAGE expression was associated with a worse survival (p=0.05). Multivariate analysis confirmed this association, which is independent of TNM stage and other clinicopathologic variables. In conclusion, the detection of GAGE gene expression by RT-PCR appears to be an independent survival predictor in completely resected NSCLC patients.

摘要

MAGE、BAGE和GAGE基因编码由T细胞定义的肿瘤相关抗原(TAA),这些抗原在多种人类肿瘤中表达,而在正常组织中沉默。由于它们的表达模式,这些TAA作为主动免疫治疗的潜在靶点和分子肿瘤标志物受到关注。这两个特征在改善非小细胞肺癌(NSCLC)的治疗中都可能有用。我们通过逆转录聚合酶链反应(RT-PCR)分析了46例接受了根治性切除且中位随访期为41个月的NSCLC患者队列中MAGE、BAGE和GAGE基因家族某些成员的表达情况。相当一部分(范围为25%-41%)的NSCLC表达MAGE-A1、-A2、-A3、GAGE-1、-2、-8和MAGE-B2基因。相反,BAGE和MAGE-B1的表达频率较低(分别为17%和11%)。总体而言,59%的NSCLC患者表达至少一种基因,因此可能符合肿瘤特异性免疫治疗方案的条件。此外,虽然MAGE-A、BAGE和MAGE-B基因未提供任何预后信息,但GAGE表达与较差的生存率相关(p=0.05)。多变量分析证实了这种关联,该关联独立于TNM分期和其他临床病理变量。总之,通过RT-PCR检测GAGE基因表达似乎是完全切除的NSCLC患者的一个独立生存预测指标。

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