复发转移大肠癌中K-Ras基因表达及其临床意义

Expression and clinical significance of K-Ras gene in advanced colorectal cancer

目的探讨K-Ras基因在复发转移大肠癌中的表达、临床意义及其对预后的预测价值。方法收集2005年1月至2010年12月解放军总医院收治的复发转移大肠癌病例资料,回顾性分析所有患者临床病理特征、分子特征与预后的关系。结果入选96例病例,K-Ras基因突变率为25%(24/96),性别、年龄、病灶部位、病理类型、转移器官个数、转移部位与K-Ras基因突变无相关性。截至2010年12月31日,70例(72.9%)患者病情进展,29例(30.2%)死亡,中位总生存期(OS)为37.39个月,中位无进展生存期(PFS)为9.63个月,1、2、3年生存率分别为79%、57%和52%。单因素分析显示K-Ras基因状态(P=0.004)、肝转移(P=0.002)及辅助化疗(P=0.012)是影响PFS的预后因素,其他临床病理特征及一线治疗应用靶向药对PFS无明显影响;年龄(P=0.026)、肝转移(P=0.050)、腹腔转移(P=0.001)及全程用靶向药物(P=0.009)是影响OS的预后因素,其他临床病理特征、K-Ras基因状态以及辅助化疗对OS无影响。分层分析显示,K-Ras野生组中使用西妥昔单抗者较未使用者OS明显延长(P=0.019)。Cox多因素分析显示肝转移(P=0.002)和K-Ras基因状态(P=0.004)是PFS的独立预后因素;肝转移(P=0.003)、腹腔转移(P=0.000)和全程用靶向药物(P=0.007)是OS的独立预后因素。结论复发转移大肠癌K-Ras野生型患者能从西妥昔单抗治疗中获益,K-Ras基因检测是西妥昔单抗疗效的预测指标;K-Ras野生型患者对化疗的受益程度高于突变型患者,K-Ras基因状态可以预测化疗疗效。

Objective To explore the expression and clinical significance of K-Ras gene in advanced colorectal cancer and discuss its value of prognosis predicting.Methods All the advanced colorectal cancer patients who received treatment in PLA General Hospital from January 2005 to December 2010 were retrospectively evaluated.The relationships among clinicopathologic parameters,biomarkers＇ expressions and survival were analyzed.Results Ninety-six patients were enrolled.Twenty-four patients（25%） had K-Ras mutation.There were no significant differences in all clinicopathological parameters between the wild-type K-Ras group and the mutant type group.Until the destination of study,70 cases got progression（72.9%） and 29 cases（30.2%） died.The median overall survival（OS）was 37.39 months,and the median progression-free survival（PFS） was 9.63 months.The 1-,2-,and 3-year survival rate was 79%,57% and 52% respectively.Univariate analysis showed that the wild-type K-Ras group（P=0.004）,no hepatic metastasis group（P=0.002） and the adjuvant chemotherapy group（P=0.012） presented better PFS.The differences in PFS were not statistically significant in other clinicopathologic parameters and targeted therapy in first-line treatment.Young age group（P=0.026）,no hepatic metastasis group（P=0.050）,no celiac metastasis group（P=0.001） and the group received targeted therapy（P=0.009） predicted better OS.The differences in OS were not statistically significant in other clinicopathologic parameters,K-Ras status and adjuvant chemotherapy group.Stratified analysis indicated that those received cetuximab-containing regimen presented better OS than those unreceived（P=0.019） in wild-type K-Ras group.Cox proportional hazard regression model showed that hepatic metastasis（P=0.002）and K-Ras status（P=0.004）were the independent factors affecting the PFS.Hepatic metastasis（P=0.003）,celiac metastasis（P=0.000）and targeted therapy（P=0.007）were the independent factors affecting the OS in advanced colorectal cancer patients.Conclusion In advanced colorectal cancer,patients with wild-type K-Ras could benefit from cetuximab in combination with chemotherapy,so the detection of K-Ras gene can predict the effect of cetuximab-containing regimen.The ones with wild-type K-Ras benefit more from chemotherapy than mutant ones.The K-Ras status may be helpful in predicting the chemotherapy effect.