非小细胞肺癌化疗敏感性与 EML4-ALK 、 EGFR 、KRAS 、 c-MET 基因状态的关系

Correlation analysis between chemotherapy sensitivity and EML4-ALK, EGFR, KRAS and c-MET gene mutation in non-small cell lung cancer

摘要:

目的??探究非小细胞肺癌化疗敏感性与棘皮动物微管相关类蛋白 4- 间变淋巴瘤激酶 （ EML4 - ALK ） 融合基因、表皮生长因子受体（ EGFR ） 、 KRAS 及 c-MET 基因状态的相关性。方法??选取 2015 年 1 月— 2018 年 1 月在江西省宜春市人民医院就诊的非小细胞肺癌患者资料，根据肺局部淋巴结转移情况，参照第 8 版肺癌 TNM 分期，入组Ⅲ期 b 至Ⅳ期患者 96 例。采用 ARMS 血浆 EGFR 、 ALK 、 KRAS 、 c-MET 基因突变 分析方法，对外周血循环肿瘤 DNA 中目标基因状况进行检测。结果??EGFR 突变患者化疗总有效 12 例，有 效率为 24% ； EGFR 野生型患者中包括 16 例肺腺癌患者和 30 例肺鳞癌患者，化疗总有效 21 例，有效率为 45.65% ； 两组发生严重化疗毒副作用数比较，差异无统计学意义（ P >0.05） 。 AML4-ALK 融合突变患者化疗 总有效 4 例，有效率 100% ； 无 AML4-ALK 融合突变患者化疗总有效 28 例，有效率 30.77%，两组化疗有效 率差异有统计学意义（ P <0.05） ，两组发生严重化疗毒副作用数比较，差异无统计学意义（ P >0.05） 。 KRAS 突变患者均肺腺癌患者，化疗总有效 6 例，有效率 75% ； 88 例 KRAS 无突变患者化疗总有效 27 例，有效率 30.68%，两组化疗有效率差异有统计学意义（ P >0.05） ； 两组发生严重化疗毒副作用数比较，差异有统计学意 义 （ P >0.05） 。 c-MET 突变患者化疗总有效2例， 有效率12.5% （2例/16例） ； c-MET 无突变患者化疗总有效31例， 有效率 38.75% ； 两组发生严重化疗毒副作用数比较， 差异无统计学意义（ P >0.05） 。结论?? EML4-ALK、KRAS 和 MET 基因的状态均影响患者的化疗效果。

Abstract:

Objective To investigate the correlation between chemotherapy sensitivity and EML4-ALK, EGFR, KRAS and c-MET gene mutation in non-small cell lung cancer. Methods Patients with non-small cell lung cancer who were admitted in our hospital were involved in this study. Totally 96 stage IIIb and IV patients were enrolled. Totally 10 ml vein blood was collected for determination of ARMS, EGFR, ALK, KRAS and c-MET gene mutation. Results Effective rate of chemotherapy was 24% in patients with mutations in EGFR (n = 12) while effect rate was 45.65% in patients with wild type of EGFR (n = 46). No significant difference in serious side effect was identified between the two groups (P > 0.05). Effective rate of chemotherapy was 100% in patients with AML4-ALK (n = 4) fusion mutation while effect rate was significantly decreased in patients without AML4-ALK fusion (n = 48) (30.77% Vs 100%, P < 0.05). No significant difference in serious side effect was identified between the two groups (P > 0.05). Effective rate of chemotherapy was 75% in patients with KRAS mutation (n = 6) while effect rate was significantly decreased in patients without AML4-ALK fusion (n = 27) (175% Vs 30.68%, P < 0.05). The serious side effects of chemotherapy and chemotherapy have statistically significant different. Effective rate of chemotherapy was 12.5% in patients with mutations in c-MET (n = 4) while effect rate was 38.75% in patients with wild type of EGFR (n = 31). No significant difference in serious side effect was identified between the two groups (P > 0.05). Conclusions Mutation in EML4-ALK, KRAS, MET may affect the efficacy of chemotherapy in patients with non-small cell lung cancer.