论文部分内容阅读
目的鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,KRAS)是非小细胞肺癌(non-small cell lung cancer,NSCLC)的重要驱动基因之一,KRAS基因状态在晚期NSCLC患者一线化疗疗效中的预测作用尚未明确。本研究旨在探讨晚期NSCLC患者KRAS基因状态和一线化疗疗效的关系。方法回顾性分析郑州大学第一附属医院2014-07-10-2015-12-01收治经组织病理学确诊的205例表皮生长因子受体(epidermal growth factor receptor,EGFR)阴性的晚期NSCLC患者临床资料。随访至2015-12-31,排除随访丢失的患者,185例患者纳入本研究。分析KRAS基因状态、临床特征、化疗疗效及无疾病进展生存期(progression-free survival,PFS)之间的关系。结果 185例患者均进行了KRAS基因检测,KRAS基因突变患者44例(23.8%),野生型为141例(76.2%)。KRAS基因突变类型分别为G12D(36.4%)、G12A(25.0%)、G12C(15.9%)、G12V(13.6%)、G12R(6.8%)和G13D(2.3%)。全部患者均接受一线铂类为基础的化疗,客观缓解率(objective response rate,ORR)为24.3%,疾病控制率(disease control rat,DCR)为62.2%。KRAS野生型患者的DCR为63.8%,略高于突变型患者的56.8%,差异无统计学意义,χ2=0.701,P=0.477。KRAS突变患者培美曲塞化疗组中男性的ORR为52.2%,高于女性的12.5%,差异有统计学意义,χ2=6.454,P=0.011;男性的DCR为82.6%,明显高于女性的31.2%,差异有统计学意义,χ2=10.516,P=0.001。KRAS基因野生型患者的中位PFS为4.3个月,显著长于突变组患者的3.7个月,差异有统计学意义,χ2=21.982,P<0.01;而KRAS各突变亚型之间的PFS相比较,差异无统计学意义,χ2=5.110,P=0.403。Cox回归多因素分析显示,KRAS基因突变是影响PFS的预后因素,HR=2.152,95%CI:1.513~3.062,P<0.01。结论 KRAS突变是晚期NSCLC患者一线化疗PFS的负性预后因素,KRAS突变患者中男性对以培美曲塞为基础的化疗反应更好。
Objective KRAS is one of the most important driving genes in non-small cell lung cancer (NSCLC). The prediction of the KRAS status in the first-line chemotherapy in patients with advanced NSCLC The role is not yet clear. The aim of this study was to investigate the relationship between KRAS status and the efficacy of first-line chemotherapy in patients with advanced NSCLC. Methods Retrospective analysis of the First Affiliated Hospital of Zhengzhou University 2014-07-10-2015-12-01 Clinical data of 205 patients with advanced NSCLC who were negative for epidermal growth factor receptor (EGFR) confirmed by histopathology . Follow-up to December 31, 2015, excluding patients with missed follow-up, 185 patients were included in the study. The relationship between KRAS gene status, clinical features, chemotherapy efficacy and progression-free survival (PFS) was analyzed. Results All 185 patients underwent KRAS gene detection. There were 44 patients (23.8%) with KRAS mutation and 141 (76.2%) patients with wild type. The types of KRAS mutations were G12D (36.4%), G12A (25.0%), G12C (15.9%), G12V (13.6%), G12R (6.8%) and G13D (2.3%). All patients received first-line platinum-based chemotherapy with an objective response rate (ORR) of 24.3% and a disease control rate (DCR) of 62.2%. The DCR of KRAS wild type patients was 63.8%, slightly higher than 56.8% of the mutant patients, the difference was not statistically significant (χ2 = 0.701, P = 0.477). The ORR rate of male patients with KRAS mutation in pemetrexed chemotherapy group was 52.2%, which was higher than that in female patients (χ2 = 6.454, P = 0.011). The male DCR was 82.6%, which was significantly higher than that in female 31.2%, the difference was statistically significant, χ2 = 10.516, P = 0.001. The median PFS of KRAS gene wild type patients was 4.3 months, which was significantly longer than 3.7 months in patients with mutation group, the difference was statistically significant, χ2 = 21.982, P <0.01; compared with the PFS of the KRAS mutation subtypes , The difference was not statistically significant, χ2 = 5.110, P = 0.403. Cox regression multivariate analysis showed that KRAS gene mutation was the prognostic factor of PFS, HR = 2.152, 95% CI: 1.513 ~ 3.062, P <0.01. Conclusions KRAS mutation is a negative prognostic factor for first-line PFS in patients with advanced NSCLC. Men with KRAS mutations respond better to pemetrexed-based chemotherapy.