Longitudinal Analysis and Prognostic Effect of Cancer-Testis Antigen Expression in Multiple Myeloma
Longitudinal Analysis and Prognostic Effect of Cancer-Testis Antigen Expression in Multiple Myeloma
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DOI：
10.1158/1078-0432.ccr-08-0989
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发表时间：
2009-02-15
影响因子：
11.5
通讯作者：
Kroeger, Nicolaus
中科院分区：
文献类型：
--
作者：
Atanackovic, Djordje;Luetkens, Tim;Kroeger, Nicolaus
目的：关于癌症-睾丸（CT）抗原的肿瘤表达随时间的持续性的可靠数据以及CT抗原表达对恶性肿瘤的临床过程的影响的后续分析对于它们作为诊断标志物和免疫学靶标的评价是至关重要的。应用常规逆转录PCR、实时PCR和Western印迹，我们首次对多发性骨髓瘤CT抗原表达进行了纵向研究，分析了129例患者的330份骨髓样本中4种CT抗原的表达结果：CT抗原频繁且令人惊讶地持续表达，表明这些免疫原性靶标的下调并不代表骨髓瘤中常见的肿瘤逃逸机制。我们观察到CT抗原表达水平与骨髓瘤患者的临床病程有很强的相关性，如骨髓驻留浆细胞数量和外周副蛋白水平所示，这表明CT抗原作为独立的肿瘤标志物的作用。在研究骨髓瘤患者异基因干细胞移植后CT抗原表达的预后价值时，我们发现MAGE-Cl等基因的表达是早期复发和生存率显著降低的重要指标。我们的研究结果表明，CT抗原可能促进多发性骨髓瘤的进展，特别是MAGE-C1/CT 7，其似乎对其它CT抗原起到“看门人”基因的作用，可能表征更恶性的表型。重要的是，我们的研究还强烈支持CT抗原作为诊断和预后标志物以及骨髓瘤治疗靶点的有用性。
Purpose: Reliable data on the persistence of tumor expression of cancer-testis (CT) antigens over time and consequent analyses of the effect of CT antigen expression on the clinical course of malignancies are crucial for their evaluation as diagnostic markers and immunotherapeutic targets.Experimental Design: Applying conventional reverse transcription-PCR, real-time PCR, and Western blot, we did the first longitudinal study of CT antigen expression in multiple myeloma analyzing 330 bone marrow samples from 129 patients for the expression of four CT antigens (MAGE-C1/CT7 MAGE-C2/CT10, MAGE-A3, and SSX-2).Results: CT antigens were frequently and surprisingly persistently expressed, indicating that down-regulation of these immunogenic targets does not represent a common tumor escape mechanism in myeloma. We observed strong correlations of CT antigen expression levels with the clinical course of myeloma patients as indicated by the number of bone marrow-residing plasma cells and peripheral paraprotein levels, suggesting a role for CT antigens as independent tumor markers. Investigating the prognostic value of CT antigen expression in myeloma patients after allogeneic stem cell transplantation, we found that expression of genes, such as MAGE-Cl, represents an important indicator of early relapse and dramatically reduced survival.Conclusions: Our findings suggest that CT antigens might promote the progression of multiple myeloma and especially MAGE-C1/CT7, which seems to play the role of a "gatekeeper" gene for other CT antigens, might characterize a more malignant phenotype. Importantly, our study also strongly supports the usefulness of CT antigens as diagnostic and prognostic markers as well as therapeutic targets in myeloma.