BMC Cancer:预测转移性结直肠癌药物反应新发现

2014-11-30 MedSci MedSci原创

爱尔兰圣文森大学医院和都柏林大学生命科学院等处的科学家进行了一项蛋白质组学研究,旨在评估不同的蛋白表达是否能区分对化疗和贝伐单抗有反应的患者,及探讨所选定蛋白表达与患者生存率的关系,相关研究成果在线发表于近期的BMC Cancer杂志上。

贝伐单抗(Avastin),一种人源化的血管内皮生长因子单克隆抗体,可改善转移性结直肠癌(mCRC)患者的无进展生存率(PFS)和总体生存率(OS),但目前还没有生物标志物可预测患者对该药物治疗的反应情况。

爱尔兰圣文森大学医院和都柏林大学生命科学院等处的科学家进行了一项蛋白质组学研究,旨在评估不同的蛋白表达是否能区分对化疗和贝伐单抗有反应的患者,及探讨所选定蛋白表达与患者生存率的关系,相关研究成果在线发表于近期的BMC Cancer杂志上。

该研究基于患者无进展生存率,将接受化疗和贝伐单抗治疗的转移性结直肠癌患者预处理的血清样本分为应答组和无应答组。研究对血清样本进行了免疫亲和性清除,并采用双向差异凝胶电泳(2D-DIGE)分析蛋白表达情况,及LC-MS/MS分析法进行蛋白鉴定。研究最后还利用ELISA和免疫组化法对所选择的蛋白在一个更大患者群(n=68和n=95)的血清和组织样本基础上分别进行了验证。

研究结果显示,LC-MS/MS分析法鉴定出68种蛋白在两组之间差异表达。其中三种蛋白(载脂蛋白E(APOE)、血管紧张素原(AGT)和维生素D结合蛋白(DBP))被选定进行有效性研究。研究发现,间质组织中增加的APOE表达与较短的无进展生存率(p=0.0001)和总体生存率(p=0.01)有关,DBP表达与较短的总体生存率有关(p=0.037)。在上皮组织中,增加的APOE表达与较长的无进展生存率和总体生存率有关(p<0.05),AGT上皮表达与较长的无进展生存率有关(p< 0.05)。增加的血清AGT浓度与较短的总体生存率有关(p=0.009)。

这项研究认为,被鉴定出来的载脂蛋白E(APOE)、血管紧张素原(AGT)和维生素D结合蛋白(DBP)与接受化疗和贝伐单抗治疗的转移性结直肠癌患者生存结局密切相关。但研究同时指出,在确定这些蛋白标志物应用临床之前,还需要更大患者群样本对这些蛋白的特性行进一步研究。

原始出处:

Petra Martin, Sinead Noonan, Michael P Mullen, et al. Predicting response to vascular endothelial growth factor inhibitor and chemotherapy in metastatic colorectal cancer. BMC Cancer 2014, 14:887, doi:10.1186/1471-2407-14-887.


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