Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer
Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer
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DOI：
10.1158/1078-0432.ccr-05-1203
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发表时间：
2005-11-15
影响因子：
11.5
通讯作者：
Altorki, NK
中科院分区：
文献类型：
--
作者：
Gure, AO;Chua, R;Altorki, NK
目的：定位于X染色体的癌症-睾丸基因具有共同的表达模式，并对表观遗传机制的调节剂表现出相似的反应。我们想知道癌基因与睾丸基因的表达是否协调发生，以及它是否与非小细胞肺癌（NSCLC）的疾病变量和临床结局相关。实验设计：通过半定量PCR评价了523例接受手术的NSCLC患者肿瘤中9种癌-睾丸基因（NY-ESO-1、拉格-1、MAGE-A1、MAGE-A3、MAGE-A4、MAGE-A10、CT 7/MAGE-C1、SSX 2和SSX 4）的表达。447例患者的临床数据被用来关联癌症睾丸表达变量的疾病和临床outcome.Results：至少有一个癌症睾丸基因表达的鳞状细胞癌，62%的细支气管肺泡癌，腺癌样本的67%。在36个可能的癌症-睾丸组合中，有34个观察到统计学显著的共表达。睾丸癌基因的表达，无论是累积的还是单独的，都与男性性别、吸烟史、晚期肿瘤、淋巴结和病理分期、胸膜浸润和无毛玻璃样阴影有显著相关性。考克斯回归分析显示NY-ESC-1和MAGEA 3的表达是预后不良的标志物，与肺腺癌的混杂变量无关。结论：癌-睾丸基因在NSCLC中协同表达，其表达与疾病进展和预后不良有关。
Purpose: Cancer-testis genes mapping to the X chromosome have common expression patterns and show similar responses to modulators of epigenetic mechanisms. We asked whether cancertestis gene expression occurred coordinately, and whether it correlated with variables of disease and clinical outcome of non-small cell lung cancer (NSCLC). ExperimentalDesign: Tumors from 523 NSCLC patients undergoing surgery were evaluated for the expression of nine cancer-testis genes (NY-ESO-1, LAGE-1, MAGE-A1 MAGE-A3, MAGE-A4, MAGE-A10, CT7/MAGE-C1, SSX2, and SSX4) by semiquantitative PCR. Clinical data available for 447 patients were used to correlate cancer-testis expression to variables of disease and clinical outcome.Results: At least one cancer-testis gene was expressed by 90% of squamous carcinoma, 62% of bronchioloalveolar cancer, and 67% of adenocarcinoma samples. Statistically significant coexpression was observed for 34 of the 36 possible cancer-testis combinations. Cancer-testis gene expression, either cumulatively or individually, showed significant associations with male sex, smoking history, advanced tumor, nodal and pathologic stages, pleural invasion, and the absence of ground glass opacity. Cox regression analysis revealed the expression of NY-ESC-1 and MAGEA3 as markers of poor prognosis, independent of confounding variables for adenocarcinoma of the lung.Conclusions: Cancer-testis genes are coordinately expressed in NSCLC, and their expression is associated with advanced disease and poor outcome.