论文部分内容阅读
目的:通过检测局部晚期乳腺癌患者新辅助化疗前后的血清凝溶胶蛋白前体(gelsolin,GSN)和α-1-酸性糖蛋白1前体(alpha-1-acid glycoprotein 1precursor,ORM1)变化,从蛋白质组学的角度探索乳腺癌的化疗耐药机制并寻找一种能够评价乳腺癌化疗耐药性的血清蛋白标志。方法:选取烟台毓璜顶医院肿瘤内科2008-01-01-2010-01-01接受新辅助化疗的局部晚期乳腺癌患者共30例,根据化疗疗效分为敏感组和耐药组。耐药组6例,敏感组24例。留取化疗前后血清进行双向凝胶电泳,得到化疗前后在耐药组血清中特异表达的差异蛋白质点,应用基质辅助激光解析电离飞行时间质谱(MALDI-TOF-TOF)技术对获得的差异蛋白质胶点进行质谱鉴定,得到耐药组的差异蛋白,应用蛋白质印迹法验证差异蛋白的变化趋势。结果:从耐药组血清中共筛选、鉴定出13个差异蛋白质,上调蛋白7个,下调蛋白6个。其中GSN化疗后下调,ORM1化疗后上调。应用蛋白质印迹法验证,结果显示这2个蛋白的变化与其在蛋白质组学中的表现一致。结论:乳腺癌耐药组患者化疗后血清GSN下调,ORM1上调,这2个蛋白可能与乳腺癌化疗耐药机制有关,可能作为评价乳腺癌化疗耐药性的血清标志。
Objective: To detect the changes of gelsolin (GSN) and alpha-1-acid glycoprotein 1 precursor (ORM1) in neoadjuvant chemotherapy in patients with locally advanced breast cancer, Proteomics perspective explore the chemoresistance mechanism of breast cancer and look for a serum protein marker that can evaluate the chemoresistance of breast cancer. Methods: Totally 30 patients with locally advanced breast cancer receiving neoadjuvant chemotherapy were enrolled in the Department of Oncology, Yuhuangding Hospital, Yantai. The patients were divided into sensitive group and resistant group according to the curative effect. Drug-resistant group of 6 cases, sensitive group of 24 cases. Before and after chemotherapy, the serum was separated by two-dimensional gel electrophoresis to obtain the differentially expressed protein spots in the serum of the drug-resistant group before and after chemotherapy. The differences of the obtained protein-protein gel were analyzed by using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF- Point mass spectrometry to identify the differential proteins in the drug-resistant group, the changes of the differential proteins were verified by Western blotting. Results: A total of 13 differential proteins, 7 proteins were up-regulated and 6 proteins were down-regulated. Which GSN after chemotherapy down, ORM1 chemotherapy after the increase. Using Western blotting, the results showed that the changes of these two proteins were consistent with their performance in proteomics. Conclusions: Serum GSN is down-regulated and ORM1 is up-regulated in patients with drug-resistant breast cancer, which may be related to the mechanism of chemoresistance in breast cancer and may be used as a serum marker to evaluate the chemoresistance of breast cancer.