Bcl-2 样蛋白 11 缺失多态性可预测晚期非小细胞肺癌的生存。

Bcl-2-like protein 11 deletion polymorphism predicts survival in advanced non-small-cell lung cancer.

机构信息

*Department of Oncology; †National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital; ‡Graduate Institute of Oncology and Cancer Research Center; §Graduate Institute of Clinical Medicine; ‖College of Medicine; ¶College of Life Science, National Taiwan University; #Institute of Statistical Science, Academia Sinica; **Department of Medical Imaging; and ††Department of Internal Medicine, National Taiwan University Hospital, Taiwan.

出版信息

J Thorac Oncol. 2014 Sep;9(9):1385-92. doi: 10.1097/JTO.0000000000000238.

DOI:10.1097/JTO.0000000000000238

PMID:25057939

Abstract

INTRODUCTION

Germline Bcl-2-like protein 11 (BIM) deletion polymorphism in Asian is a poor predictive factor for treatment outcomes to tyrosine kinase inhibitors (TKIs) in malignancies. We explored the impact of BIM deletion polymorphism on treatment outcome of advanced non-small-cell lung cancer (NSCLC).

METHODS

We prospectively collected tissue samples, blood, and clinical data from two cohorts of advanced NSCLC patients. BIM deletion polymorphism was correlated with overall survival (OS) and progression-free survival (PFS) to epidermal growth factor receptor (EGFR) TKIs and chemotherapy treatment.

RESULTS

BIM deletion polymorphism was detected in blood of 16.2% (33 of 204) patients. The PFS to first-line EGFR-TKIs in 153 patients were 8.6 and 4.6 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.004). Among 120 patients who received chemotherapies, the PFS to chemotherapies were 5.6 and 3.5 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.050). The OS of all 204 patients was 24.8 and 16.8 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.005). Multivariate analyses suggested that BIM deletion polymorphism was an independent predictor for shorter PFS to EGFR-TKIs (hazard ratio [HR] 2.15, p = 0.002), PFS to chemotherapy (HR 2.40, p = 0.016), and OS (HR 1.65, p = 0.039).

CONCLUSIONS

BIM deletion polymorphism predicts shorter PFS to EGFR-TKIs and OS in advanced NSCLC.

摘要

简介

亚洲人种的 Bcl-2 样蛋白 11（BIM）缺失多态性是酪氨酸激酶抑制剂（TKIs）治疗恶性肿瘤疗效的不良预测因素。我们探讨了 BIM 缺失多态性对晚期非小细胞肺癌（NSCLC）治疗结果的影响。

方法

我们前瞻性地收集了两个晚期 NSCLC 患者队列的组织样本、血液和临床数据。将 BIM 缺失多态性与表皮生长因子受体（EGFR）TKIs 和化疗治疗的总生存期（OS）和无进展生存期（PFS）相关联。

结果

在 204 名患者中，有 16.2%（33 名）检测到 BIM 缺失多态性。在 153 名接受一线 EGFR-TKIs 治疗的患者中，野生型 BIM 和 BIM 缺失多态性患者的 PFS 分别为 8.6 和 4.6 个月（p = 0.004）。在 120 名接受化疗的患者中，野生型 BIM 和 BIM 缺失多态性患者的 PFS 分别为 5.6 和 3.5 个月（p = 0.050）。204 名患者的 OS 分别为野生型 BIM 和 BIM 缺失多态性患者的 24.8 和 16.8 个月（p = 0.005）。多变量分析表明，BIM 缺失多态性是 EGFR-TKIs（风险比 [HR] 2.15，p = 0.002）、化疗 PFS（HR 2.40，p = 0.016）和 OS（HR 1.65，p = 0.039）较短的独立预测因子。