XAGE-1 expression in non-small cell lung cancer and antibody response in patients
XAGE-1 expression in non-small cell lung cancer and antibody response in patients
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DOI：
10.1158/1078-0432.ccr-05-0216
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发表时间：
2005-08-01
影响因子：
11.5
通讯作者：
Nakayama, E
中科院分区：
文献类型：
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作者：
Nakagawa, K;Noguchi, Y;Nakayama, E
目的：XAGE-1最初是通过使用表达序列标签数据库搜索PAGE/GAGE相关基因而被鉴定的，并被证明具有癌症/睾丸样抗原的特征。到目前为止，已鉴定出四个转录本变体XAGE-1a、XAGE-1b、XAGE-1c和XAGE-1d。我们最近发现XAGE-1b是肺腺癌患者血清识别的优势抗原。我们研究了四种XAGE-1变异体在非小细胞肺癌(NSCLC)中的表达及XAGE-1蛋白表达。实验设计：采用常规30周期实时定量逆转录聚合酶链式反应和免疫组织化学方法检测49例非小细胞肺癌组织中4种XAGE-1基因转录变异体的表达情况。结果：49例肺癌患者血清中分别有15例和6例检测到XAGE-1b和XAGE-1d的表达。未见XAGE-1a和XAGE-1c基因表达。XAGE-1bmRNA在31例腺癌中表达14例(45%)，在18例其他组织类型肺癌中表达1例(6%)。用XAGE-1单抗进行免疫组织化学分析，15例XAGE-1bmRNA阳性标本中有14例表达XAGE-1蛋白，34例XAGE-1bmRNA阴性标本中有3例表达XAGE-1蛋白。结论：XAGE-1b在肺腺癌中高表达，且呈免疫原性，提示XAGE-1b是一种很有前途的抗肺腺癌免疫治疗抗原。
Purpose: XAGE-1 was originally identified by the search for PAGE/GAGE-related genes using expressed sequence tag database and was shown to exhibit characteristics of cancer/testis-like antigens. Four transcript variants XAGE-1a, XAGE-1b, XAGE-1c, and XAGE-1d have been identified thus far. We recently identified XAGE-1b as a dominant antigen recognized by sera from lung adenocarcinoma patients. We here investigated the mRNA expression of four XAGE-1 variants and XAGE-1 protein expression in non-small cell lung cancer (NSCLC). Humoral immune response to XAGE-1b was also evaluated in patients.Experimental Design: Forty-nine NSCLC specimens were analyzed for the expression of four XAGE-1 transcript variants by conventional 30-cycle and real-time reverse transcription-PCR and XAGE-1 protein expression by immunohistochemistry. Sera from 74 patients were analyzed for XAGE-1b antibody production by ELISA and Western blot.Results: XAGE-1b and XAGE-1d mRNA were detected in 15 and 6 of 49 lung cancer specimens, respectively. No XAGE-1a or XAGE-1c mRNA expression was observed. XAGE-1b mRNA expression was observed in 14 of 31 (45%) adenocarcinoma and 1 of 18 (6%) lung cancer with other histologic types. Immunohistochemical analysis using a XAGE-1 monoclonal antibody showed that 14 of 15 XAGE-1b mRNA-positive and 3 of 34 XAGE-1b mRNA-negative specimens expressed XAGE-1 protein. Seropositivity was observed in 5 of 56 patients with adenocarcinoma, whereas none of 18 patients with other histologic types produced XAGE-1b antibody.Conclusion: XAGE-1b is highly and strongly expressed in lung adenocarcinoma and immunogenic in patients, suggesting that XAGE-1b is a promising antigen for immunotherapy against lung adenocarcinoma.