重组人血管内皮抑制素靶向治疗非小细胞肺癌的分子生物学研究

Molecular biology research of recombinant human endostatin targeted therapy of non-small-cell lung cancer

目的探讨分子生学标记物与重组人血管内皮抑制素靶向治疗非小细胞肺癌(non-small-cell lung cancer,NSCLC)疗效之间的关系。方法选择符合要求的非小细胞肺癌患者68例,随机均分为A组和B组,每组34例。A组采用多西他赛+顺铂(docetaxel and cisplatin,DP)及吉非替尼化疗,B组在A组化疗方案的基础上加用重组人血管内皮抑制素。采用免疫组化的方法检测表皮生长因子受体(epidermao growth factor receptor,EGFR)、KRAS基因(K-ras,p21)、血管内皮生长因子(vascular endothelial growthfactor,VEGF)、乳腺癌1号基因(breast cancer susceptibility gene 1,BRCA1)、棘皮动物微管相关类蛋白4与间变性淋巴瘤激酶融合基因(echinoderm mierotubule-associated protein-like-4-anaplastic lymphoma kinase,EML4-ALK)、核苷酸切除修复交叉互补1(excision repair cross complementing 1,ERCC1)、β-微管蛋白和分化抗原簇3(Cluster of differentiation 3,CD3)生物学标记物的表达情况。结合2组患者生物学标志物的表达情况和无进展生存期(progression free survival,PFS),统计出适合不同方案的人群类型。结果 B组的中位PFS较A组显著延长;无论VEGF和BRCA1低表达或高表达,B组的中位PFS较A组显著提高;ERCC1、KRAS、EML4-ALK和β-微管蛋白高表达,B组的中位PFS较A组有显著提高;EGFR和CD3低表达,B组的中位PFS较A组显著延长(P<0.05)。结论VEGF和BRCA1高表达或低表达,KRAS、ERCC1、EML4-ALK和β-微管蛋白高表达及EGFR和CD3低表达的非小细胞肺癌患者对DP及吉非替尼联合重组人血管内皮抑制素靶向治疗较为敏感。

Objective To investigate the relationship between molecular biological markers and recombinant human endostatin targeted therapy in non-small-cell lung cancer(NSCLC).Methods 68 cases patients with non-small-cell lung cancer to meet the requirements were randomly divided into group A (n=34)and group B (n=34).Group A received docetaxel and cisplatin(DP)and gefitinib;group B received recombinant human endostatin on the base of group A.The biological markers species,such as,EGFR,KRAS,VEGF,BRCA1,EML4-ALK,ERCC1,β-tubulin and CD3 were detected by immunohistochemical.The types of population for different programs were summarized according to the expression of biological markers and progression free survival (PFS)of the two groups. Results Group B median PFS was significantly longer than that in group A;no matter low or high expression of VEGF and BRCA1,group B median PFS was significantly longer than that in group A(P<0.05);high expression of ERCC1,KRAS,EML4-ALK andβ-tubulin,group B median PFS was significantly longer than that in group A(P<0.05);low expression of EGFR and CD3,group B median PFS was significantly longer than that in group A (P<0.05 ).Conclusion No matter low or high expression of VEGF and BRCA1 ,low expression of KRAS, ERCC1,EML4-ALK and β-tubulin and high expression of EGFR and CD3 in patients with non-small cell lung cancer may be more sensitive to the treatment of DP and gefitinib combined with recombinant human endostatin.