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The advantage of signal transduction as a translational research in cervical cancer after radiotherapy

信号转导作为宫颈癌放疗后转化研究的优势

基本信息

批准号：
14570885
负责人：
HARIMA Yoko
金额：
$ 2.18万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

To reveal the genes relevant for prediction of cervical cancer after radiotherapy, we carried out cDNA microarray experiments on primary cervical cancer comparing with patients in CR group and NC groups. Some of these genes had already been associated with the radiation response, such as XRCC5 which was found more in radioresistant tumors than in radiosensitive ones. Ku80 protein, which is the gene product of XRCC5, using histopathological method of formalin-fixed sections of tumor biopsies in determining tumor response to radiotherapy and survival in 89 cervical cancer patients. Ku80-negative tumors showed significantly better responses than Ku80-positive ones, comparing CR and PR/NC responses(P=0.01). In addition, overall survival was significantly better in the Ku80-negative patients as compared with those who were Ku80-positive(P=0.04).Next, to identify a set of genes related to thermoradiosensitivity of cervical carcinoma and to establish a predictive method. We compared the expression profiles of thermoradiosensitive and thermoradio-resistant tumors obtained by punch biopsy before treatment using a cDNA microarray consisting of 23,040 human genes. We selected 35 genes on the basis of a clustering analysis, arid confirmed the validity of these genes with a cross validation test. Some of these genes were already known to be associated with appptosis(BIK,TEGT,SSI-3), hypoxia-inducible gene(HIF1A,CA12), and tumor cell invasion and metastasis(CTSL,CTSB,PLAU,CD44). We developed a "Predictive Score" system that could clearly separate the thermoradiosensitive group from the thermoradioresistant one. These results may eventually lead to the achievement of "personalized therapy" for this disease.

为揭示放疗后宫颈癌发生的相关基因，我们对原发性宫颈癌患者进行了cDNA微阵列实验，并与CR组和NC组进行比较。其中一些基因已经与辐射反应相关，例如XRCC 5，它在辐射抗性肿瘤中比在辐射敏感性肿瘤中发现得更多。采用组织病理学方法检测89例宫颈癌患者放疗后肿瘤组织中XRCC 5基因产物Ku 80蛋白的表达。比较CR和PR/NC反应，Ku 80阴性肿瘤的反应显著优于Ku 80阳性肿瘤（P=0.01）。此外，Ku 80阴性患者的总生存率显著高于Ku 80阳性患者（P=0.04）。其次，筛选一组与宫颈癌热放射敏感性相关的基因，并建立预测方法。我们使用包含23，040个人类基因的cDNA微阵列比较了治疗前通过钻孔活检获得的热放射敏感性和热放射抗性肿瘤的表达谱。在聚类分析的基础上，我们选择了35个基因，并通过交叉验证检验证实了这些基因的有效性。这些基因中的一些已经被认为与凋亡（BIK、TEGT、SSI-3）、缺氧诱导基因（HIF 1A、CA 12）和肿瘤细胞侵袭和转移（CTSL、CTSB、PLAU、CD 44）相关。我们开发了一个“预测评分”系统，可以清楚地区分热辐射敏感组和热辐射耐受组。这些结果可能最终导致这种疾病的“个性化治疗”的实现。