Analysis of biomarker proteins for chemosensitivity by protein chip

发现新的癌症生物标志物对诊断和治疗癌症具有重要意义我们以前建立了一个由来自肺、胃、结肠、乳腺等8个不同器官类型的39个人类癌细胞株组成的“癌细胞系小组”。我们调查了它们的药物敏感性和基因表达谱，并将所有数据整合到一个数据库中，从数据库中我们一直在获得关于癌症分子药理学的各种独特信息。在本研究中，我们利用SELDI蛋白质芯片系统(Ciphergen)研究了39个癌细胞系的蛋白质表达谱，并分析了新的生物标志物。结果如下：1.我们发现11970 Da的蛋白在结肠癌细胞系中特异表达，并鉴定其为胸腺素原α(PT-α)。它是一种酸性核蛋白，被认为参与了细胞凋亡。2.制备抗PTa抗体，免疫组织化学检测…更多的人类结肠癌组织。其次，腺瘤中PT-α的表达水平高于正常粘膜，结肠癌组织中PT-α的表达水平甚至高于腺瘤。这是首次发现PT-DNA是一种新的候选肿瘤标志物。基于这一发现，我们希望通过检测更多的结肠癌患者其在癌组织和血液中的表达来验证PTα作为肿瘤标志物的有效性。我们也想分析它在结肠癌中的功能，以检验它是否可以成为治疗的分子靶点。3.为了寻找化疗敏感性的生物标志物，我们分析了当抗癌药物作用于癌细胞时，癌细胞中蛋白质表达谱发生了什么变化。用紫杉醇、顺铂、SN-38等9种药物作用于NCI-H2 6人肺癌细胞。在各种变化中，我们发现了几种表达水平的变化是药物特异性的蛋白质，它们是化疗敏感性的候选生物标志物。基于这一发现，我们希望将我们的研究扩展到候选蛋白质的鉴定和功能分析及其有效性。因此，使用癌细胞系面板的蛋白质芯片分析是一种有用的方法来发现生物标记物，如肿瘤标记物和化疗敏感性标记物。我们希望利用它来发展癌症的诊断和治疗。较少

Discovery of new biomarkers for diagnosis and therapy of cancer is important We previously established a "cancer cell lines panel" consisting of 39 human cancer cell lines derived from 8 different organ types, such as lung, stomach, colon, breast and so on. We have investigated their drug sensitivities and gene expression profiles and integrated all the data into a database, from which we have been getting various unique information on the molecular pharmacology of cancer. In the present study, we investigated the protein expression profiles of the 39 cancer cell lines by SELDI Proteinchip System (Ciphergen) and analyzed new biomarkers. Followings are the summary of the results.1.We found that a 11970 Da protein was expressed exclusively in colon cancer cell lines, and identified it as prothymosin α (PT-α). It is an acidic nuclear protein and suggested to be involved in apoptosis. However, its function is not known well.2.We prepared anti PT a antibodies and immunohistochemically exami … More ned human colon cancer tissue. Then, adenoma expressed PT-α at a higher level than normal mucosa, and colon cancer tissue expressed it at an even higher level than adenoma This is the first observation indicating that PT-α is a new candidate of tumor marker. On the basis of this finding, we would like to validate PT α as a tumor marker by examining the larger number of colon cancer patients for its expression in the cancer tissue and in the blood. We also would like to analyze its function in colon cancer to examine whether it could be a molecular target of therapy.3.To discover biomarkers for chemosensitiyity, we analyzed what alteration of protein expression profile occurs in cancer cells when exposed to anticancer drugs. NCI-H226 human lung cancer cells were exposed to 9 drugs, such as paclitaxel, cisplatin, and SN-38. Among various alterations, we recognized several proteins whose changes in the expression level were drug specific, which are the candidates of the biomarker for chemosensitivity. On he basis of this finding, we would like to extend our study to the identification and functional analysis of the candidate proteins and their validation.Therefore, the protein chip analysis using the cancer cell lines panel is a useful methodology for discovering biomarkers, such as tumor marker and chemosensitivity markers. We would like to exploit it for development of diagnosis and therapy of cancer. Less