ADAM8 as a novel serological and histochemical marker for lung cancer
ADAM8 as a novel serological and histochemical marker for lung cancer
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DOI：
10.1158/1078-0432.ccr-04-1436
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发表时间：
2004-12-15
影响因子：
11.5
通讯作者：
Nakamura, Y
中科院分区：
文献类型：
--
作者：
Ishikawa, N;Daigo, Y;Nakamura, Y
目的和实验设计：我们一直在研究参与肺癌发生的基因，通过检查非小细胞肺癌的基因表达谱，以确定可能作为诊断标志物或新的分子疗法的发展目标的分子。选择编码解整合素和金属蛋白酶结构域8的ADAM 8的基因作为这种分子的候选物。应用肿瘤组织芯片技术检测363例肺癌标本中ADAM 8蛋白的表达。采用酶联免疫吸附试验（ELISA）检测105例肺癌患者和72例正常对照者血清中的ADAM 8水平。结果：在绝大多数肺癌组织中，ADAM 8呈高表达。ADAM 8的高水平表达在晚期IIIB/IV期腺癌中比在I-IIIA期腺癌中更常见。肺癌患者血清ADAM 8水平显著高于健康对照组。我们的标准定义的血清ADAM 8阳性病例的比例为63%，癌胚抗原为57%，表明这两种标志物的诊断能力相当。使用ADAM 8和癌胚抗原的联合检测增加了灵敏度，因为80%的肺癌患者被诊断为阳性，而72名健康志愿者中只有11%被误诊为阳性。此外，外源性表达的ADAM 8增加了哺乳动物细胞的迁移活动，表明ADAM 8可能在肺癌的进展中发挥重要作用。结论：我们的数据表明，ADAM 8应该是有用的诊断标志物，并可能作为一个治疗靶点。
Purpose and Experimental Design: We have been investigating genes involved in pulmonary carcinogenesis by examining gene expression profiles of non-small-cell lung cancers to identify molecules that might serve as diagnostic markers or targets for development of new molecular therapies. A gene encoding ADAM8, a disintegrin and metalloproteinase domain-8, was selected as a candidate for such molecule. Tumor tissue microarray was applied to examine expression of ADAM8 protein in archival lung cancer samples from 363 patients. Serum ADAM8 levels of 105 lung cancer patients and 72 controls were also measured by ELISA. A role of ADAM8 in cellular motility was examined by Matrigel assays.Results: ADAM8 was abundantly expressed in the great majority of lung cancers examined. A high level of ADAM8 expression was significantly more common in advanced-stage IIIB/IV adenocarcinomas than in adenocarcinomas at stages I-IIIA. Serum levels of ADAM8 were significantly higher in lung cancer patients than in healthy controls. The proportion of the serum ADAM8-positive cases defined by our criteria was 63% and that for carcinoembryonic antigen was 57%, indicating equivalent diagnostic power of these two markers. A combined assay using both ADAM8 and carcinoembryonic antigen increased sensitivity because 80% of the lung cancer patients were then diagnosed as positive, whereas only 11% of 72 healthy volunteers were falsely diagnosed as positive. In addition, exogenous expression of ADAM8 increased the migratory activity of mammalian cells, an indication that ADAM8 may play a significant role in progression of lung cancer.Conclusions: Our data suggest that ADAM8 should be useful as a diagnostic marker and probably as a therapeutic target.