[Retrospective Study of Efficacy in BIM Gene Polymorphism on First-line EGFR-TKIs Treatment for Advanced Lung Adenocarcinoma]

Zhongguo Fei Ai Za Zhi. 2017 Aug 20;20(8):543-548. doi: 10.3779/j.issn.1009-3419.2017.08.08.
[Article in Chinese]

Abstract

Background: The aim of this study is to detect the BIM polymorphism in 85 formalin-fixed and parrffin-embedded (FFPE) and some blood samples of advanced lung adenocarcinoma patients and study the relativity betweenthe BIM polymorphism and tyrosine kinase inhibitor (TKI). The correlation between BIM detection of different types of specimens was discussed.

Methods: There were 85 patients who were diagnosed as advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) 19 or 21 exon mutation in thoracic surgery of Xuanwu Hospital from February 2013 to November 2014, all of who were received EGFR-TKI as first-line treatment in the study. FFPE and some blood were used to detect the BIM polymorphism. The objective response rate (ORR) and progression-free survival (PFS) of two groups were compared. According to smoking, sex, EGFR mutation and other factors, the single factor analysis was performed, and the correlation between paraffin samples and blood test BIM was compared.

Results: The ORR in BIM polymorphism and non-polymorphism groups was no significant differences (P>0.05). The median PFS in BIM polymorphism and non-polymorphism group was 7.1 months and 12.8 months, respectively (P=0.013). Univariate analysis the median PFS, women were longer than men (12.1 months vs 10.7 months, P=0.835); Non-smokers were longer than smokers (12.1 months vs 9.7 months, P=0.974). Group in EGFR exon 21 is longer than group in EGFR exon 19 (12.2 months vs 8.7 months, P=0.303).

Conclusions: Detection of BIM gene polymorphism in lung cancer patients with EGFR-TKIs treatment might be helpful for predicting prognosis. But a large sample study is needed.

背景与目的 通过对85例肺腺癌患者石蜡包埋标本及部分全血样本BIM缺失多态性的检测,分析BIM多态性与酪氨酸激酶抑制剂(tyrosine kinase inhibitors, TKIs)药物疗效相关性,初探不同类型标本BIM检测的相关性。方法 收集2013年2月-2014年11月间经宣武医院胸外科诊断明确的IIIb期-IV期肺腺癌患者,表皮生长因子受体(epidermal growth factor receptor, EGFR)19或21外显子突变85例,给予一线TKIs治疗,采用石蜡组织标本和部分全血进行BIM基因多态性检测,分析两组患者治疗客观有效率(objective response rate, ORR)、无进展生存期(progression-free survival, PFS),并根据吸烟、性别、EGFR突变位点等因素进行单因素分析,同时对比石蜡标本与血液检测BIM的相关性。结果 在受检的85例FFPE样本中,BIM基因具有缺失多态性14例(16.47%),纯和无缺失多态性71例(83.53%)。在13例对照样本中,石蜡样本和血液样本检出BIM基因缺失多态性2例,且为相同患者样本。BIM多态性的患者在用药物后的客观缓解率与无多态性组无统计学差异(P>0.05)。BIM基因缺失多态性、纯和无缺失患者接受药物治疗的中位PFS分别为7.1个月、12.8个月,存在统计学差异(P=0.013)。男性和女性中位PFS(10.7个月、12.1个月,P=0.835)、吸烟组和非吸烟组中位PFS(9.7个月、12.1个月,P=0.974)、EGFR 19和21外显子中位PFS(8.7个月、12.2个月,P=0.303)比较均无统计学差异(P>0.05)。结论 检测患者BIM基因多态性对晚期肺腺癌 EGFR-TKIs治疗患者的评估预后可能有一定参考意义,但需要进行大样本的研究。.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Bcl-2-Like Protein 11 / genetics*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Exons
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation
  • Polymorphism, Genetic
  • Protein Kinase Inhibitors / administration & dosage*
  • Retrospective Studies

Substances

  • Bcl-2-Like Protein 11
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors

Grants and funding

本研究受国家重点基础研究发展计划—中国人类蛋白质组草图(No. 2014CBA02004)资助