晚期EGFR突变肺腺癌Ki-67表达与EGFR-TKIs治疗疗效的相关性

The relationship between Ki-67 expression and the treatment efficacy of EGFR-TKIs in EGFR-mutated advanced lung adenocarcinoma

目的:分析晚期EGFR突变型肺腺癌(LADC)组织中Ki-67表达和其他临床病理特征与EGFR-TKIs客观疗效和生存预后的相关性。方法:回顾性分析2017年05月至2020年05月我院102例晚期EGFR突变型LADC中Ki-67表达情况与其他临床特征,所有患者均接受第一代EGFR-TKIs 6周后进行客观疗效评价,无进展生存期(progression-free survival,PFS)为主要研究终点。结果:Ki-67表达可较为准确地预测EGFR-TKIs的客观缓解率(object response rate,ORR)[AUC=0.7690(0.6705~0.8675),P<0.0001],Ki-67表达与EGFR-TKIs客观疗效呈负性相关(P=0.000),分期(P=0.170)、EGFR-TKIs(P=0.112)、ECOG PS(P=0.551)、EGFR突变(P=0.163)与ORR无明显相关。Ki-67高表达相对低表达,可显著缩短PFS(P<0.0001);单因素分析发现ECOG PS(HR 1.740,P=0.001)、EGFR突变(HR 1.656,P=0.023)、分期(HR 1.487,P=0.005)、Ki-67表达(HR 1.027,P=0.000)为影响PFS的相关因素;多因素分析发现,Ki-67表达(HR 1.040,P=0.000)为影响PFS的独立预后因素。结论:晚期EGFR突变型LADC组织中Ki-67高表达可降低EGFR-TKIs的ORR,缩短PFS,Ki-67表达在晚期EGFR突变LADC中的意义值得进一步探索。

Objective:To analyze the relationship of Ki-67 expression and other clinical characteristics and object response and prognosis in patients with EGFR-mutated advanced lung adenocarcinoma(LADC).Methods:We retrospectively analysed the Ki-67 expression and other clinical features in 102 patients with EGFR-mutated advanced LADC at our hospital from May 2017 to May 2020.All patients were treated with first-generation EGFR-TKIs.The curative effect was evaluated after every six weeks.Progression-free survival(PFS)was used as the endpoint of this study.Results:The Ki-67 expression could accurately predict the objective response rate(ORR)of EGFR-TKIs[area under the curve(AUC)=0.7690,95% confidence interval(CI):0.6705~0.8695,P<0.0001].Ki-67 expression was negatively correlated with the ORR of EGFR-TKIs(P=0.000),and stage(P=0.170),EGFR-TKIs(P=0.112),ECOG PS(P=0.551),and EGFR mutation status(P=0.163)were not significantly correlated with ORR.The overexpression of Ki-67 was a negative prognostic factor for PFS in EGFR-mutated advanced LADC(P<0.0001).According to univariate analysis,ECOG PS(HR 1.740,P=0.001),EGFR mutation(HR 1.656,P=0.023),stage(HR 1.487,P=0.005),and Ki-67 expression(HR 1.027,P=0.000)were prognostic factors of PFS.According to the multivariate Cox analysis,Ki-67 expression(HR 1.040,P=0.000)was a prognostic factor of PFS.Conclusion:High Ki-67 expression might shorten the ORR and PFS ofEGFR-TKIs in patients with EGFR-mutated advanced LADC.Ki-67,as a promising prognostic biomarker forEGFR-mutated advanced LADC,deserves more attention from researchers.