BIM 缺失对接受 EGFR-TKIs 治疗的 EGFR 突变型 NSCLC 患者预后的影响：一项荟萃分析。

Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis.

机构信息

Department of Respiratory, Characteristic Medical Center of People's Armed Police Force, Tianjin 300162, China.

Department of Immunology, Characteristic Medical Center of People's Armed Police Force, Tianjin 300162, China.

出版信息

Biomed Res Int. 2021 Oct 13;2021:3621828. doi: 10.1155/2021/3621828. eCollection 2021.

DOI:10.1155/2021/3621828

PMID:34722761

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8551980/

Abstract

BACKGROUND

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis.

METHODS

Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed.

RESULTS

A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS (HR = 1.35, 95% CI: 1.10-1.64, = 0.003) and a tendency toward an unfavorable OS (HR = 1.22, 95% CI: 0.99-1.50, = 0.068). Patients with deletion polymorphism had lower ORR (OR = 0.60, 95% CI: 0.42-0.85, = 0.004) and DCR (OR = 0.59, 95% CI: 0.38-0.90, = 0.014) compared with those without deletion.

CONCLUSION

BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.

摘要

背景

表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）耐药在表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）患者中不可避免。Bcl-2 样蛋白 11（BIM）的胚系 2903bp 缺失多态性导致促凋亡 BH3 仅有 BIM 蛋白表达减少，并阻止了肿瘤细胞对 TKI 诱导的凋亡。然而，这种缺失多态性与 EGFR-TKI 治疗反应之间的关联在临床观察中仍然不一致。因此，我们进行了本次荟萃分析。

方法

通过检索 PubMed、Embase 和 ClinicalTrials.gov 数据库，我们在 2021 年 3 月 31 日前确定了符合条件的研究。使用随机效应模型计算无进展生存期（PFS）和总生存期（OS）的风险比（HRs）和 95%置信区间（CIs）、客观缓解率（ORR）和疾病控制率（DCR）的比值比（ORs）和 95%置信区间（CIs）。还进行了敏感性分析、荟萃回归分析和发表偏倚分析。

结果

共有 20 项研究（来自 18 项研究的 3003 名接受 EGFR-TKIs 治疗的 EGFR 突变型 NSCLC 患者）纳入本研究。475 名（15.8%）患者存在 BIM 基因内含子 2903bp 缺失，2528 名（84.2%）患者为野生型。BIM 缺失预测 PFS 显著缩短（HR=1.35，95%CI：1.10-1.64， =0.003），OS 有不利趋势（HR=1.22，95%CI：0.99-1.50， =0.068）。与无缺失的患者相比，携带缺失多态性的患者 ORR（OR=0.60，95%CI：0.42-0.85， =0.004）和 DCR（OR=0.59，95%CI：0.38-0.90， =0.014）较低。