K-ras基因突变对Ⅲ期大肠癌术后辅助化疗疗效的预测意义

Role of K-ras mutation in predicting therapeutic effect of adjuvant chemotherapy on postoperative stage Ⅲ colorectal cancer

  • 摘要: 目的 探讨K-ras基因突变与接受术后辅助化疗的Ⅲ期大肠癌患者预后的关系。 方法 收集2005年1月-2010年12月在我院接受手术治疗及术后辅助化疗的Ⅲ期大肠癌病例40例,采用PCR扩增和DNA测序技术检测K-ras第12、13位密码子的突变情况,分析患者临床病理特征、分子特征与生存规律的关系。 结果 K-ras基因突变率为15%(6/40),性别、年龄、病灶部位、病理分级、病理类型、T分期、N分期与K-ras基因突变无相关性。截至2010年12月31日,34例(85%)出现复发转移,9例(22.5%)死亡,中位总生存期(overall survival,OS)48.460个月,中位无疾病生存期(disease-freesurvival,DFS)11.992个月,1年、3年、5年生存率分别为97%、73%、51%。单因素分析显示K-ras野生组较突变组DFS显著延长(P<0.001),而其余病理特征对DFS无明显影响;年龄(P=0.037)、病理分级(P=0.015)及1年内是否复发转移(P=0.010)是影响OS的预后因素,而其余病理特征及K-ras基因状态对OS无影响。COX多因素分析显示K-ras基因状态(P<0.001)是DFS的独立预后因素;年龄(P=0.010)和1年内是否复发转移(P=0.006)是OS的独立预后因素。 结论 对于接受手术治疗及以氟尿嘧啶为基础的术后辅助化疗Ⅲ期大肠癌患者,K-ras野生型患者的DFS优于突变型患者,提示K-ras基因可能是预测Ⅲ期大肠癌患者术后辅助化疗疗效的指标。

     

    Abstract: Objective To study the correlation between K-ras mutation and prognosis of patients with stageⅢ colorectal cancer(CRC) receiving postoperative adjuvant chemotherapy. Methods Forty patients with stageⅢ CRC who underwent operation and postoperative adjuvant chemotherapy from January 2005 to December 2010 in our hospital were enrolled in this study.Their K-ras mutation on codons 12 and 13 was detected by PCR and DNA sequencing.Correlation between clinicopathologic and molecular characteristics and survival time was analyzed. Results The K-ras mutation rate was 15%(6/40).The gender and age of patients,site,pathological grade and type,T and N staging of the disease were not related with the K-ras mutation.Thirty-four patients(85%) had recurrence or metastasis and 9 patients(22.5%) died from January 2005 to December 2010.The median overall survival(OS) time was 48.460 months,the median disease-free survival(DFS) time was 11.992 months,the 1-,3-,and 5-year survival rate was 97%,73% and 51%,respectively.Univariate analysis showed that the DFS time of patients with wild-type K-ras was longer than that of those with mutant K-ras(P<0.001).The other pathological parameters had no effect on the DFS time.However,the age of patients,pathological grade and recurrence or metastasis within 1 year were the factors influencing the OS,while the other pathological parameters and K-ras mutation had no effect on the OS.Cox multivariate analysis showed that the K-ras status was an independent risk factor for the DFS time,while the age of patients and recurrence or metastasis of the disease within 1 year(P=0.006) were the independent risk factors for the OS. Conclusion The DFS time of colorectal cancer patients with wild-type K-ras receiving postoperative adjuvant chemotherapy is longer than that of those with mutant K-ras,indicating that the K-ras gene can be used as an indication for the therapeutic effect of adjuvant chemotherapy on postoperative colorectal cancer.

     

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