乳腺癌患者血清GSN与ORM1差异表达与化疗耐药相关性初步研究

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a-1-酸性糖蛋白1前体（alpha-1-acidglycoprotein1precursor，ORMl）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-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200801-01-2010-01-01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并蛋白质点，应用基质辅助激光解析电离飞行时间质谱（MAI，DI-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-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。

Relationship on the difference expression of gelsolin precursor,alpha-l-acid glycoprotein 1 precursor and chemotherapy drug resistance in breast cancer

OBJECTIVE： To detect the changes in protein of breast cancer before and after the neoadjuvant chemotherapy,so as to explore the mechanism of breast cancer chemotherapy drug resistance by proteomics and to find serum protein marker of breast cancer to evaluate the chemotherapy drug resistance. METHODS： The data of 30 locally advanced breast cancer patients who had accepted neoadjuvant chemotherapy was collected between 1st. January 2008 and 1st. January 2010,in Department of Oncology Yantai Yuhuangding Hospital. The patients were divided into resistant and sensitive groups according to the curative effect of chemotherapy. Resistant group were 6 cases and sensitive group 24 cases. Fasting serum specimens were obtained before and after the chemotherapy. Two way gel electrophoresis was used to get the gel maps of the serum specimens and gel analysis software was used to analysis the image maps, screen the protein points which differentially expressed before and after chemotherapy. Serum protein were identified in the way of matrix auxiliary laser disintegrate series time of flight mass spectrometer （MALDI-TOF TOF） technology for the protein glue points. RESULTS： Thirteen differences protein were obtained from the serum of resistant group in breast cancer. Among them, seven were upregulated proteins,six were downregulated proteins. Ggelsolin Precursor was downregulated and Alpha-1 acid glycoprotein 1 precursor was upregulated after neoadjuvant chemotherapy in resistance group. Western imprinting method was used to test the variation trend before and after chemotherapy. The variation trend of western imprinting method and the proteomics results were consistent. CONCLUSIONS：Gelsolin Precursor was downregulated and Alpha-l-acid glycoprotein 1 precursor was upregulated after neoadjuvant chemotherapy in resistance group. The two proteins may be associated with breast cancer chemotherapy drug resistance mechanism and may be as the serum markers to evaluate the chemotherapy drug resistance in breast cancer.