Recursive partitioning as an approach to selection of immune markers for tumor diagnosis.
Recursive partitioning as an approach to selection of immune markers for tumor diagnosis.
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发表时间：
2003-11
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通讯作者：
J. Koziol;Jian-ying Zhang;C. Casiano;Xuan Peng;F. Shi;A. Feng;E. Chan;E. Tan
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作者：
J. Koziol;Jian-ying Zhang;C. Casiano;Xuan Peng;F. Shi;A. Feng;E. Chan;E. Tan
目的和实验设计癌症血清含有与称为肿瘤相关抗原（TAA）的一组独特的自体细胞抗原反应的抗体，但是针对任何单个抗原的阳性反应的低频率已经排除了将自身抗体用作有用的诊断标记。采用酶免疫分析法，我们检测了527名癌症患者（64名乳腺癌患者，45名结直肠癌患者，91名胃癌患者，65名肝细胞癌患者，56名肺癌患者和206名前列腺癌患者）和346名正常人中7种TAA，c-myc，细胞周期蛋白B1，IMP 1，Koc，p53，p62和生存素的抗体频率。我们使用递归分割来评估我们是否可以根据每个个体对七种TAA的抗体反应性特征将个体准确地分类为癌症患者或正常人。结果递归划分导致选择七组TAA的子集，其在肿瘤和对照之间进行区分，并且这些子集对于每个癌症队列是独特的。当使用正常均值+2 SD作为免疫测定阳性的标准截止值时，分类树在癌症队列中的灵敏度范围为0.77至0.92，特异性范围为0.85至0.91。细胞周期蛋白B1抗体是胃癌和肺癌以及肝细胞癌的初始鉴别节点，并且是所有其他癌症队列中的后续鉴别节点。c-myc在乳腺癌中是最初的鉴别节点，p62在前列腺癌中是最初的鉴别节点，IMP 1在结肠癌中是最初的鉴别节点。递归划分表明，任何癌症队列都不需要7种TAA中的3种以上来达到这些灵敏度和特异性水平。结论：初步研究表明，多抗原微阵列可以为癌症检测和诊断提供准确和有价值的工具。微阵列的性能可以通过适当选择用于不同癌症群组的TAA的其他组合来增强。
PURPOSE AND EXPERIMENTAL DESIGN Cancer sera contain antibodies which react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs), but the low frequency of positive reactions against any individual antigen has precluded use of autoantibodies as useful diagnostic markers. With enzyme immunoassay, we examined antibody frequencies to a panel of seven TAAs, c-myc, cyclin B1, IMP1, Koc, p53, p62, and survivin, in 527 cancer patients (64 breast cancer patients, 45 colorectal cancers, 91 gastric cancers, 65 hepatocellular carcinomas, 56 lung cancers, and 206 prostate cancers), and 346 normals. We used recursive partitioning to assess whether we could accurately classify individuals as either cancer patients or normals on the basis of the profile of antibody reactivity to the seven TAAs for each individual. RESULTS Recursive partitioning resulted in the selection of subsets of the seven-panel TAA, which differentiated between tumors and controls, and these subsets were unique to each cancer cohort. The classification trees had sensitivities ranging from 0.77 to 0.92 and specificities ranging from 0.85 to 0.91 in the cancer cohorts when normal means +2 SDs were used as standard cutoffs for immunoassay positivity. Antibody to cyclin B1 was the initial discriminating node for gastric and lung cancers, and for hepatocellular carcinoma, and was a subsequent discriminating node in all of the other cancer cohorts. c-myc was the initial discriminating node in breast cancer, p62 in prostate cancer, and IMP1 in colon cancer. Recursive partitioning demonstrated that no more than three of the seven TAAs were needed for any cancer cohort to arrive at these levels of sensitivity and specificity. CONCLUSIONS This initial study shows that multiple antigen miniarrays can provide accurate and valuable tools for cancer detection and diagnosis. Performance of the miniarrays might be enhanced by other combinations of TAAs appropriately selected for different cancer cohorts.