J Thorac Oncol：晚期非小细胞肺癌患者生存的新预测因子
来源：生物谷 2014-08-24 13:36
2014年8月25日讯 /生物谷BIOON/--根据在Journal of Thoracic Oncology杂志的一项新研究发现，接受表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）或化疗治疗的亚洲晚期非小细胞肺癌（NSCLC）患者Bcl-2蛋白样蛋白11
2014年8月25日讯 /生物谷BIOON/--根据在Journal of Thoracic Oncology杂志的一项新研究发现，接受表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）或化疗治疗的亚洲晚期非小细胞肺癌（NSCLC）患者Bcl-2蛋白样蛋白11（BIM）的缺失，与患者更短的无进展生存期（PFS）相关。此外，BIM的缺失可独立预测晚期非小细胞肺癌患者的总生存期（OS）。
BIM蛋白可以激活细胞程序性死亡，也即细胞凋亡途径。 BIM的缺失已经在12.8％的亚洲人中被检测到，但在高加索人群中很少看到。非小细胞肺癌的所有患者接受有针对性的任何治疗或化疗治疗，最终会在不同时间段失败。
研究人员在National Taiwan University Hospital检查，BIM缺失对接受EGFR酪氨酸激酶抑制剂或化疗治疗的204例晚期非小细胞肺癌患者生存预后的影响。
研究表明对于表皮生长因子受体酪氨酸激酶抑制剂治疗的患者，BIM的缺失是较短PFS的一个独立预测因子（危险比=2.15，P = 0.002），BIM缺失患者的中位PFS为4.6个月，BIM野生型患者为8.6个月。
同时，对于化疗治疗的BIM缺失患者，中位PFS为3.5，BIM野生型患者为5.6个月。BIM的缺失也独立预测总体生存率（危险比=1.65，P = 0.039）。（生物谷Bioon.com）
Clinical Significance of BIM Deletion Polymorphism in Non–Small-Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation
Isobe, Kazutoshi MD,et al.
Background:
Germline alterations in the proapoptotic protein Bcl-2–like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non–small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations.
Methods:
We studied 70 patients with EGFR mutation-positive non–small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion.
Results:
BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864–8.547; p < 0.001).
Conclusions:
Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.
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