【作者】 徐柯；

【导师】 潘宏铭；

【作者基本信息】 浙江大学 ， 肿瘤学， 2009， 硕士

【摘要】 背景与目的K-ras基因突变在结直肠癌的发生发展过程中起着重要的作用,检测K-ras基因状态及其表达产物对判断结直肠癌预后有重要意义,尤其在预测表皮生长因子受体抑制剂西妥昔单抗治疗晚期结直肠癌患者的疗效时更为重要。本研究总结了结直肠癌患者手术标本K-ras基因突变情况与临床、病理特征、术后复发率的关系,并且观察西妥昔单抗联合化疗在术后复发转移的结直肠癌二线及二线以后治疗中的疗效,及其与K-ras基因状态的关系。研究方法本文回顾性分析了邵逸夫医院27例晚期结直肠癌患者的病理标本,采用焦磷酸测序技术检测其K-ras基因突变情况,并且总结K-ras基因状态与临床、病理特征、术后复发率的关系;其中10例患者曾应用西妥昔单抗联合化疗进行复发转移后二线及二线以后治疗,观察治疗效果、不良反应及其与K-ras基因状态的关系。结果在27例行K-ras基因检测的患者中,野生型17例,突变型10例,突变率为37.0%,其中12密码子突变5例,13密码子突变5例,K-ras基因突变情况与其临床、病理特征、术后复发率没有明显相关性。其中10例术后复发转移性晚期结直肠癌患者应用西妥昔单抗联合化疗行二线及二线以上化疗,无1例患者达到CR,PR2例,SD5例,PD3例,在6例K-ras基因野生型患者中,PR2例,SD3例,PD1例,在4例K-ras基因突变型患者中,PRO例,SD2例,PD2例。结论本研究中晚期结直肠癌患者的K-ras基因突变率和相关报道一致,K-ras基因状态是预测西妥昔单抗联合治疗晚期结直肠癌有效性的重要指标。更多还原

【Abstract】 Background and purpose:K-ras gene plays an important role in the progress of colorectal cancer.K-ras detection can be used for determining prognosis of colorectal cancer,especially for predicting the efficacy of Cetuximab treatment in advanced colorectal cancer.This study summarized the association among K-ras mutation,tumor characteristics and relapse rate after surgery,and also explored the efficacy of Cetuximab in the second/third-line treatment.Methods:Tissue samples of 27 colorectal cancer patients from Sir Run Run Shaw Hospital were analyzed to detect K-ras gene mutation by using Pyrosequencing method.10 of these patients were treated with Cetuximab combined with second/third-line chemotherapy,and were analyzed the relationship of K-ras gene and efficacy of Cetuximab plus chemotherapy.Results:There ware 17 wild-type and 10 mutated-type K-ras gene in all 27 cases with mutation rate of 37%.5 mutations occurred in codon12,and 5 in codon13.Mutations were not associated with clinical and pathologic characters,postoperation recurrent rate. Of the 10 cases who treated with Cetuximab,there were no complete response(CR),2 partial response(PR),5 stable disease(SD) and 3 progressive disease(PD).Of the 6 wild-type K-ras cases,there were no complete response(CR),2 partial response(PR),3 stable disease(SD) and 1 progressive disease(PD).Of the 4 mutated-type K-ras cases, there were no complete response(CR),no partial response(PR),2 stable disease(SD) and 2 progressive disease(PD).Conclusion:The mutation rate of the K-ras gene was similar with other reports.K-ras gene is an important biomarker for determining prognosis of colorectal cancer.更多还原