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目的:应用表面加强激光解析电离化飞行时间质谱技术(surface enhanced laser desorption/ionization-time of flight-mass spectrometry,SELDI-TOF-MS)比较乳腺癌曲妥珠单抗治疗耐药患者与非耐药患者血清蛋白质谱的差异,筛选预测乳腺癌患者曲妥珠单抗耐药的标志蛋白。方法:选择福建省肿瘤医院2008年1月至2009年10月曲妥珠单抗治疗的乳腺癌患者35例,以临床界定标准将患者分为耐药组(11例)和非耐药组(24例)。应用SELDI-TOF-MS技术检测两组患者外周血蛋白质表达谱的差异,以差异蛋白峰值比1.5为耐药的蛋白界定标准,以此标准判定患者耐药与否。分析该蛋白界定标准评判曲妥珠单抗耐药的灵敏度、特异度以及阳性预测值、阴性预测值。结果:以临床界定标准评判的曲妥珠单抗耐药的发生与患者年龄、分期、腋窝淋巴结转移和ER/PR双阴无关。临床耐药组和非耐药组患者外周血蛋白质表达谱比较显示,耐药患者的蛋白质峰7971Da、9284Da显著降低(P<0.05)。以蛋白界定标准评判患者曲妥单抗耐药与非耐药,7971Da评判时的灵敏度为81.82%(9/11)、特异度为83.33%(20/24)、阳性预测值为69.23%(9/13)、阴性预测值为90.91%(20/22);以9284Da评判时的灵敏度为72.73%(8/11)、特异度为79.17%(19/24)、阳性预测值为61.54%(8/13)、阴性预测值为86.36%(19/22)。结论:应用SELDI-TOF-MS技术检测的差异蛋白质峰7971Da、9284Da似可作为预测乳腺癌患者曲妥珠单抗耐药的生物标志物。
OBJECTIVE: To compare the efficacy and safety of trastuzumab-resistant breast cancer patients and non-drug-resistant breast cancer patients by surface enhanced laser desorption / ionization-time of flight-mass spectrometry (SELDI-TOF-MS) Patients with serum protein profiles of differences, screening predictors of trastuzumab resistant breast cancer marker protein. Methods: Thirty-five patients with breast cancer treated with trastuzumab from January 2008 to October 2009 in Fujian Cancer Hospital were divided into three groups: drug-resistant group (n = 11) and non-drug-resistant group 24 cases). SELDI-TOF-MS technique was used to detect the difference of protein expression profiles in peripheral blood between the two groups. The protein with the peak of differential protein was more than 1.5, and the standard was used to determine the drug resistance of the patients. The sensitivity, specificity, positive predictive value, and negative predictive value of trastuzumab resistance were evaluated by the defined criteria of the protein. RESULTS: Trastuzumab resistance was assessed by clinical criteria and was independent of patient age, staging, axillary lymph node metastasis, and ER / PR double yin. The protein expression profiles of peripheral blood in clinical drug-resistant group and non-drug-resistant group showed that the protein peaks of 7971Da and 9284Da in drug-resistant patients were significantly decreased (P <0.05). The resistance to trastuzumab was evaluated by protein-bound criteria. The sensitivity of 7971Da was 81.82% (9/11), the specificity was 83.33% (20/24) and the positive predictive value was 69.23% (9 / 13), and the negative predictive value was 90.91% (20/22). The sensitivity at 9284Da was 72.73% (8/11), the specificity was 79.17% (19/24) and the positive predictive value was 61.54% (8 / 13), negative predictive value was 86.36% (19/22). Conclusion: The differential protein peak detected by SELDI-TOF-MS technique is 7971Da. 9284Da may be used as a biomarker to predict trastuzumab resistance in breast cancer patients.