BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations.
BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations.
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DOI：
10.18632/oncotarget.12112
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发表时间：
2016-09-19
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影响因子：
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通讯作者：
on behalf of the CLICaP
中科院分区：
文献类型：
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作者：
Cardona AF;Rojas L;Wills B;Arrieta O;Carranza H;Vargas C;Otero J;Corrales-Rodriguez L;Martín C;Reguart N;Archila P;Rodríguez J;Cuello M;Ortíz C;Franco S;Rolfo C;Rosell R;on behalf of the CLICaP
促凋亡蛋白Bcl-2样11（BIM）的种系改变在不同的肿瘤中具有至关重要的作用。为了确定检测BIM缺失多态性（par 4226 bp/par 363 bp）在EGFR阳性非小细胞肺癌（NSCLC）中的临床效用，我们检查了有和没有BIM改变的患者的结果。14例患者（15.7%）存在BIM缺失。携带和不携带BIM-del的患者在临床特征或EGFR突变类型方面无显著差异;然而，携带BIM-del的患者对厄洛替尼的总体缓解率（ORR）较差（42.9% vs.无BIM-del的患者73.3%; p=0.024）以及无进展生存期（PFS）显著缩短（10.8 BIM-del+ vs.无BIM-del的患者为21.7个月; p=0.029）和总生存期（OS）（15.5 BIM-del+ vs.无BIM-del的患者为34.0个月; p=0.035）。多变量考克斯回归分析显示，BIM-del+是PFS（HR 3.0; 95%CI 1.2-7.6; p=0.01）和OS（HR 3.4; 95%CI 1.4-8.3; p=0.006）较短的独立指标。我们研究了2009年1月至2014年11月期间接受厄洛替尼治疗的89例EGFR突变的西班牙裔NSCLC患者。采用PCR方法对福尔马林固定石蜡包埋（FFPE）的肿瘤活检组织进行BIM缺失多态性（BIM-del）分析。我们回顾性分析了有和无BIM-del患者的临床特征、缓解率、毒性和结局。在西班牙裔患者中发现的BIM-del的发生率与先前在亚洲描述的相似。这种改变与厄洛替尼的不良临床反应相关，是EGFR突变NSCLC患者的独立预后因素。
Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations. BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIM-del; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006). We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM-del. The incidence of BIM-del found in Hispanic patients is similar to that previously described in Asia. This alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for patients who had NSCLC with an EGFR mutation.