基于超高效液相色谱-四级杆/静电场轨道阱高分辨质谱技术的曲妥珠单抗辅助治疗人类表皮生长因子受体-2阳性乳腺癌血清代谢组学研究

Serum metabonomics of trastuzumab in adjuvant therapy based on ultra-high performance liquid chromatography coupled to quadrupole high-resolution orbital ion trap mass spectrometry for human epidermal growth factor receptor-2-positive breast cancer

目的采用代谢组学技术,筛选可以用于预测曲妥珠单抗辅助治疗人类表皮生长因子受体-2(HER-2)阳性乳腺癌疗效的生物标志物。方法收集2017年1月至2019年12月金华市人民医院治疗的乳腺癌患者60例的血清样本,分为化疗组(30例)和化疗+曲妥珠单抗治疗组(30例),分别采用超高效液相色谱-四级杆/静电场轨道阱高分辨质谱(UHPLC-Q-Orbitrap HRMS)技术和SIMCA 14.1软件中的多元变量模式对样本及数据进行检测和分析。结果两组代谢物构建的正交偏最小二乘判别分析(OPLS-DA)模型稳健性良好,以P<0.05且VIP>1.0为筛选条件,筛选并鉴定出8个差异代谢物,可用于预测曲妥珠单抗辅助治疗HER-2阳性乳腺癌的疗效。结论代谢组学技术可揭示化疗+曲妥珠单抗组治疗HER-2阳性乳腺癌血清中内源性代谢物的变化特点,筛选出的生物标志物可用于疗效预测,同时为研究曲妥珠单抗的疗效评价提供新思路。

Objective To screen the biomarkers that can be used to predict the efficacy of trastuzumab in adjuvant treatment of human epidermal growth factor receptor-2-positive breast cancer by metabonomics.Methods Serum samples of 60 patients with human epidermal growth factor receptor-2-positive breast cancer who received treatment in Jinhua People's Hospital from January 2017 to December 2019 were retrospectively analyzed.These serum samples were divided into a chemotherapy group(n=30)and a chemotherapy+trastuzumab group(n=30).Two groups of samples were analyzed using the ultra-high performance liquid chromatography coupled to quadrupole high-resolution orbital ion trap mass spectrometry(UHPLC-Q-Orbitrap-HRMS)technique and the SIMCA 14.1 software.Results The multivariate orthogonal partial least squares-discrimination analysis(OPLS-DA)models constructed to verify differences in metabolites between the two groups had good reliability.Taking P<0.05 and VIP>1.0 as the screening conditions,eight different metabolites were screened and identified.Therefore,the constructed OPLS-DA models could be used to predict the efficacy of trastuzumab in the adjuvant treatment of human epidermal growth factor receptor-2-positive breast cancer.Conclusion Metabonomics technology can reveal the changes in serum endogenous metabolites in patients with human epidermal growth factor receptor-2-positive breast cancer who receive chemotherapy combined with trastuzumab.The selected biomarkers can be used to predict the curative effect and provide a new idea for evaluating the efficacy of trastuzumab.