Cancer/testis antigen expression as a predictor for epidermal growth factor receptor mutation and prognosis in lung adenocarcinoma
Cancer/testis antigen expression as a predictor for epidermal growth factor receptor mutation and prognosis in lung adenocarcinoma
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DOI：
10.1093/ejcts/ezs426
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发表时间：
2013-04-01
影响因子：
3.4
通讯作者：
Tanaka, Fumihiro
中科院分区：
文献类型：
--
作者：
Baba, Tetsuro;Shiota, Hironobu;Tanaka, Fumihiro
靶向癌症/睾丸（CT）抗原的免疫疗法改善了几种类型的实体瘤的存活率。CT抗原的表达与非小细胞肺癌（NSCLC）的不良生存率有关。表皮生长因子受体（EGFR）突变是肺腺癌对酪氨酸激酶抑制剂敏感性的最佳预测因子。本研究旨在探讨CT抗原表达与临床病理因素（包括EGFR突变）之间的关系，并分析其与肺腺癌预后的关系。其中125例因标本太小而无法提取足够的DNA和/或RNA，2例同时存在另一种组织学类型的肺癌被排除。共对154例患者进行了审查。采用聚合酶链反应（PCR）方法检测CT抗原（黑色素瘤相关抗原基因[法师]-A4和KK LC-1）的表达及EGFR激活突变（外显子21的L 858 R点突变和外显子19的框内缺失），MAGE-A4和KK LC-1在腺癌中的表达分别为9%（14/54）和35%（54/54）。在64例患者（42%）中发现EGFR激活突变。单变量和多变量分析表明，表达至少一种CT抗原的肿瘤与EGFR突变无关（比值比= 0.3; 95%置信区间，0.14-0.71; P < 0.01）。对135例肿瘤全切除患者进行生存分析，CT抗原阳性表达者5年生存率为71.1%，阴性表达者5年生存率为83.2%（P < 0.04），EGFR激活突变和CT抗原两个不同的治疗靶点之间呈负相关。
Immune therapy targeting cancer/testis (CT) antigens improve the survival in several types of solid tumours. The expression of CT antigens is related to poor survival in non-small-cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutation is the best predictive factor for the sensitivity to tyrosine kinase inhibitors in lung adenocarcinoma. The aim of this study was to elucidate the correlation between the expression of CT antigens and clinicopathological factors, including the EGFR mutation, and to analyse the prognosis in lung adenocarcinoma.Data were collected from a total of 281 lung adenocarcinoma patients who underwent surgery. Among them, 125 cases, whose specimens were too small to extract sufficient DNA and/or RNA, and 2 cases with the coexistence of another histological lung cancer were excluded. A total of 154 patients were reviewed. The expression of CT antigens (melanoma-associated antigen gene [MAGE]-A4 and KK-LC-1) and the EGFR-activating mutation (L858R point mutation in exon 21 and inframe deletion in exon 19) was evaluated by using polymerase chain reaction amplification.The expression of MAGE-A4 and KK-LC-1 was detected in 14 (9%) and 54 patients (35%) with adenocarcinoma. The EGFR-activating mutation was found in 64 patients (42%). Univariate and multivariate analyses demonstrated that tumours expressing at least one CT antigen were associated with no EGFR mutation (odds ratio = 0.3; 95% confidence interval, 0.14-0.71; P < 0.01). A survival analysis was performed in 135 patients who underwent complete resection and the 5-year overall survival rate was 71.1% in those with any expression of CT antigens and 83.2% in those without expression of the genes (P < 0.04).Two different therapeutic targets, EGFR-activating mutation and CT antigen, have a negative relationship with each other.