建立microRNA预测FOLFOX方案治疗晚期结直肠癌疗效模型的研究

项目名称： 建立microRNA预测FOLFOX方案治疗晚期结直肠癌疗效模型的研究

项目编号： No.81472785

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 白春梅

作者单位： 中国医学科学院北京协和医院

项目金额： 74万元

中文摘要： 结直肠癌是最常见的消化道恶性肿瘤，诊断时III/IV期患者占60%以上，化疗是治疗晚期结直肠癌的基石。FOLFOX方案（氟尿嘧啶联合奥沙利铂）是治疗晚期结直肠癌的首选方案，但其有效率仅为40-50%。寻找新的预测化疗疗效的分子生物标志物是肿瘤研究领域中一个重要目标。任一药物的作用模式都有多个基因的参与，通过对多种基因的检测建立疗效预测模型较单一基因的预测方式更加合理。本研究根据FOLFOX方案治疗晚期结直肠癌有效和无效患者肿瘤组织的microRNA差异表达结果，挑选部分microRNA构造判别模型，将具有随访结果的IV期结直肠癌患者肿瘤组织的microRNA表达水平作为训练集，使用支持向量机软件作为工具，训练判别模型，选择已知化疗疗效患者验证模型的正确率，从而建立microRNA预测FOLFOX方案治疗晚期结直肠癌疗效的模型，并用于指导晚期结直肠癌的个体化治疗。

中文关键词： microRNA；结肠癌；FOLFOX方案；模式识别

英文摘要： Coloretal cancer（CRC） is the most common malignanct neoplasm of digesetive tract. In recent years，CRC incidence rates have risen rapidly in China. CRC has already become the third most common cancer diagnosed both in man and women. More than 60% CRC cases have stage III／IV disease when diagnosed, and chemotherapy remains to be the milestone of treatment for advanced CRC. FOLFOX regimen (a chemotherapy regimen made up of the following drugs: fluorouracil, leucovorin and oxaliplatin) is one of the standard first-line therapy for advanced CRC with response rate of 40％ to 50％. This unsatisfacotry therapeutic efficacy underscores the importance of discovering novel molecular biomarkers to predict chemotherapy benefit. Since the mechanism of action of anti-cancer drugs involves various genes，it seems more reasonable to establish a prediction model of chemotherapy efficacy using multiple genes than single gene. In this research, we performed microRNA microarray on tumor block from patients with advanced CRC who received first-line FOLFOX treatment and identified differential expression of miRNAs between responsive group and non-responsive group. Those miRNAs which were significantly associated with efficacy were selected to establish a discrimination model. Then, we educated the discrimination model via Support Vector Machine software, using miRNA expression level from tumor tissue of stage IV CRC patients with follow-up information as training set. Finally, we validate the model in a larger cohort of CRC patients with definitive outcome after FOLFOX treatment. We believe that this microRNA model for predicting FOLFOX regimen efficacy will be helpful to guide the personalized treatment in advanced CRC.

英文关键词： microRNA;Coloretal cancer;FOLFOX regimen;Pattern Recognition