KRT 19 基因多态性对化疗联合靶向治疗NSCLC 疗效的影响

Effect of KRT19 gene polymorphism on efficacy of chemotherapy combined with targeted therapy for non-small cell lung cancer

摘要:

目的 探讨细胞角蛋白19 片段（KRT 19）基因多态性与化疗联合靶向治疗非小细胞肺癌（NSCLC） 疗效的相关性。方法 对146 例接受化疗联合靶向治疗的晚期NSCLC 患者进行临床疗效评价，采用PCRRFLF 分析KRT 19（-99G>C）基因，分析不同基因型与化疗联合靶向治疗疗效的相关性。结果 KRT 19 （-99G>C）中GG 基因型患者与GC+CC 基因型患者的化疗联合靶向治疗的有效率比较，差异有统计学意 义（P <0.05）；携带C 基因型者对化疗联合靶向治疗的敏感性是T 基因型的1.897 倍[Ol ^ R=1.897（95%CI ： 1.103，3.647）P =0.001] ；KRT 19（-99G>C）等位基因C 携带者（GC+CC）的MST 短于GG 基因型携带者 （P <0.05）。Cox 模型分析显示，KRT 19（-99G>C）变异等位基因C 是影响晚期NSCLC 预后的独立危险因素， 其变异等位基因C 携带者（GC+CC）的OR 是GG 基因型携带者的2.014 倍（P <0.05）。结论 KRT 19（-99G>C） 位点基因多态性是影响晚期NSCLC 患者化疗联合靶向治疗预后的独立危险因素，且与化疗联合靶向治疗敏 感性相关。

Abstract:

Objective To investigate the association of the polymorphism of Cytokeratin 19 fragment (KRT19 ) gene with the effect of chemotherapy combined with targeted therapy for non-small cell lung cancer (NSCLC). Methods Totally 146 patients with advanced NSCLC were treated by chemotherapy combined with targeted therapy and the clinical efficacy was evaluated. Using PCR-RFLF, KRT19 (-99G>C) gene was analyzed, the relationships between different genotypes of KRT19 and the efficacy of chemotherapy combined with targeted therapy were analyzed. Results The effective rate of chemotherapy with targeted therapy was significantly different between the patients with GG genotype and those with GC+CC genotype of KRT19 (-99G>C) (P < 0.05). The chemotherapy combined with targeted therapy was 1.897 times more sensitive in the patients carrying C genotype than that in the patients carrying T genotype [Ol ^ R = 1.897 (95% CI: 1 103, 3.647), P = 0.001]. MST of the KRT19 (-99G>C) C allele carriers (GC+CC) was shorter than that of the GG genotype carriers (P < 0.05). Cox model analysis showed that the variant allele C of KRT19 (-99G>C) was the independent risk factor for the prognosis of advanced NSCLC, OR of the variant allele carriers (GC +CC) was 2.014 times that of the GG genotype carriers (P = 0.003). Conclusions KRT19 gene (-99G>C) polymorphism is the independent risk factor for the prognosis of the patients with advanced NSCLC receiving chemotherapy combined with targeted therapy, and is significantly associated with the sensitivity of chemotherapy combined with targeted therapy.