Ⅰ期非小细胞肺癌相关血清差异表达蛋白的研究

Study on Differentially Expressed Serum Proteins of Stage I Non-Small Cell Lung Cancer

目的:寻找I期非小细胞肺癌(NSCLC)与健康人血清的差异表达蛋白。方法:收集天津市胸科医院经手术、病理证实的6例I期NSCLC患者血清,等量混合后设为肺癌组;同期15例健康体检血清,等量混合后设为健康对照组。利用双向凝胶电泳(2-DE)和基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS)分离、筛选和鉴定2组间的差异表达蛋白。结果:成功获得了2组的双向凝胶电泳图谱,PDquest软件分析显示,2组间差异大于2倍的蛋白质点共有128个,质谱鉴定后确定了10种蛋白质,其中7种表达量上调,分别为α1-酸性糖蛋白、C1酯酶抑制物、血管紧张素原、转铁蛋白、转甲状腺素蛋白、间-α-胰蛋白酶抑制剂重链H2及无花果酶-3;3种表达量下调,分别为纤连蛋白、补体C4-A及补体C3。结论:应用2-DE及MALDI-TOF-MS在I期NSCLC血清中鉴定出4种与肿瘤关系密切的差异表达蛋白,可作为开发NSCLC早期诊断标志物的候选蛋白。

Objective： To seek differentially expressed serum proteins related to stage Ⅰ non-small cell lung cancer （NSCLC）. Methods： The sera so of lung cancer group were collected and equally mixed from 6 patients who were surgically and pathologically diagnosed as stage Ⅰ NSCLC in Tianjin Chest Hospital. The sera samples of control group were collected and equally mixed from 15 healthy subjects in the corresponding period. Two-dimensional gel electrophoresis （2-DE） and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS） were employed to screen and identify differentially expressed serum proteins in two groups. Results： Two-dimensional electrophoretic patterns of serum proteins were successfully obtained from sera samples of two groups. PDquest software showed that 128 differentially expressed protein spots of two groups. Ten proteins were successfully identified via peptide mass fingerprinting using MALDI-TOF-MS. Among them, 7 proteins were over expressed, including alpha-1-acid glycoprotein, C1 inhibitor, angiotensinogen, transferrin, transthyretin, inter-alpha-trypsin inhibitor heavy chain H2 and ficolin-3. Whereas three proteins were under expressed, including fibronectin, complement C4-A and complement C3. Conclusion： Four differentially expressed proteins, closely related to cancer, can be separated and identified in sera samples of patients with stage Ⅰ NSCLC by 2-DE and MALDI-TOF-MS, which may serve as candidate biomarkers for early detection of NSCLC.