[发明专利]检测FOLFOX化疗药物对于结直肠癌有效性的试剂盒

说明书

本发明涉及用于检测FOLFOX化疗药物对于结直肠癌有效性的试剂盒，包括一对检测MAP4K1基因拷贝数的扩增引物序列，一对检测CDKL4基因拷贝数的扩增引物序列以及一对检测内参基因GAPDH基因拷贝数的引物序列。通过本发明设计的试剂盒，可以快捷有效的对FOLFOX化疗药物对于结直肠癌有效性进行检测，评价该待检患者是否适合应用奥沙利铂作为一线化疗药物，为临床用药提供了有效的参考。

[技术领域]

本发明涉及用于检测FOLFOX化疗药物对于结直肠癌有效性的试剂盒。

[背景技术]

结直肠癌(CRC)是世界第三大常见的恶性肿瘤，也是由癌症引起死亡的第二大原因，严重威胁人类健康(Jemal A,Bray F,Center MM,Ferlay J,Ward E,Forman D.Globalcancer statistics.CA:a cancer journal for clinicians.2011；61(2):69-90.)。近几十年来，结直肠癌的临床结果已有显著改善，不仅是由于外科技术的进步，还要归因于引入化疗和靶向药物疗法(Moertel CG,Fleming TR,Macdonald JS,et al.Levamisole andfluorouracil for adjuvant therapy of resected colon carcinoma.The New Englandjournal of medicine.1990；322(6):352-358；Andre T,Boni C,Navarro M,etal.Improved overall survival with oxaliplatin,fluorouracil,and leucovorin asadjuvant treatment in stage II or III colon cancer in the MOSAICtrial.Journal of clinical oncology:official journal of the American Societyof Clinical Oncology.2009；27(19):3109-3116；Hurwitz HI,Fehrenbacher L,Hainsworth JD,et al.Bevacizumab in combination with fluorouracil andleucovorin:an active regimen for first-line metastatic colorectalcancer.Journal of clinical oncology:official journal of the American Societyof Clinical Oncology.2005；23(15):3502-3508；Van Cutsem E,Kohne CH,Lang I,etal.Cetuximab plus irinotecan,fluorouracil,and leucovorin as first-linetreatment for metastatic colorectal cancer:updated analysis of overallsurvival according to tumor KRAS and BRAF mutation status.Journal of clinicaloncology:official journal of the American Society of Clinical Oncology.2011；29(15):2011-2019.)。依据美国国家综合癌症网络指南(NCNN)，建议Ⅲ期结直肠癌患者在经根治性切除术后进行辅助性化疗。MOSAIC和NSABP C-07临床试验结果证明采用奥沙利铂作为一线辅助化疗的方案得到认可(Andre T,Boni C,Navarro M,et al.Improvedoverall survival with oxaliplatin,fluorouracil,and leucovorin as adjuvanttreatment in stage II or III colon cancer in the MOSAIC trial.Journal ofclinical oncology:official journal of the American Society of ClinicalOncology.2009；27(19):3109-3116；Kuebler JP,Wieand HS,O'Connell MJ,etal.Oxaliplatin combined with weekly bolus fluorouracil and leucovorin assurgical adjuvant chemotherapy for stage II and III colon cancer:results fromNSABP C-07.Journal of clinical oncology:official journal of the AmericanSociety of Clinical Oncology.2007；25(16):2198-2204.)。然而，在Ⅲ期结直肠癌患者接受含有奥沙利铂的辅助性化疗法后的三年无病生存率依旧仅有65％(Uncu D,Aksoy S,Cetin B,et al.Results of adjuvant FOLFOX regimens in stage III colorectalcancer patients:retrospective analysis of 667patients.Oncology.2013；84(4):240-245)。一个有效的治疗策略就是区分奥沙利铂辅助性化疗法中可能获益较多或获益较少的患者群体，对CRC患者进行个性化药物治疗，但目前仍缺少预测以奥沙利铂为基础的化疗药物的疗效标志物。为此，临床研究急需能够简便准确地进行预后及疗效预测的方法，为结直肠癌患者术后用药提供重要参考。