大B细胞性淋巴瘤化疗敏感性相关蛋白类型及信号通路的生物信息学研究

Bioinformatic Study on Large B Cell Lymphoma Chemosensitivity Associated Proteins Classification and Signal Pathway

目的:筛选化疗敏感性不同大B细胞淋巴瘤中差异表达蛋白,并分析其类型和相关信号通路,为淋巴瘤化疗敏感性的研究提供重要的靶蛋白。方法:通过肿瘤药物敏感试验选取化疗高敏感性和低敏感性大B细胞淋巴瘤组织,进行蛋白质组学比较研究后得出差异表达蛋白;应用GO-分析软件对差异表达蛋白进行分类和关系分析。结果:将大B细胞淋巴瘤化疗高敏感组和化疗低敏感组蛋白质经二维凝胶电泳分离的差异表达蛋白通过质谱和生物信息学分析鉴定的蛋白点52个,按生化过程分为12种蛋白,其中与代谢过程有关的蛋白最多,其次是细胞过程蛋白;按信号通路分为20余条信号通路包括凋亡信号通路、细胞周期相关通路等。按分子功能分为9类蛋白,其中结合相关蛋白最多,其次是催化活性蛋白,第三为结构蛋白。按蛋白功能分为钙结合蛋白、水解酶、氧化还原酶、磷酸酶等。按细胞内定位分为细胞外区、细胞内、核糖核蛋白复合体三类蛋白,其中细胞内蛋白数量最多,其次是核糖核蛋白复合体。根据信号通路网络图,所有差异表达蛋白以三个复杂网络区为主和四个较为简单联系网络区。结论:大B细胞性淋巴瘤的化疗敏感性与多种蛋白功能和多条信号通路的改变有关,信号通路间也存在复杂的联系。

Objective： To screen the differentially expressed proteins in large B cell lymphoma with different chemosensitivity,and analyze their types and related signaling pathways to provide the target protein involved chemotherapy sensitivity of lymphoma.Methods： The tumor drug sensitivity test was applied to distinguish high-chemosensitivity and low-chemosensitivity of large B cell lymphoma tissue for comparative proteomic study. Gene ontology（GO）analysis software was applied to analyze the differentially expressed protein classification and their relationships. Results： 52 differentially expressed proteins between high-chemosensitivity and low-chemosensitivity of large B cell lymphoma tissue were separated and identified by two-dimensional gel electrophoresis, mass spectrometry and bioinformatics analysis. The 52 proteins were classified according to the biochemical process and divided into 12 kinds of protein including metabolic processes related proteins to the most, followed by cell protein. The 52 proteins were classified according to the signal pathway and belonged to more than 20 signaling pathways, including apoptosis signaling pathway and cell cycle related pathway. Of the 52 proteins were classified according to molecular function and divided into 9 protein types with the binding related protein most, followed by the catalytic activity protein, third structural proteins. Of the 52 proteins, protein functional classification included calcium binding proteins, enzymes, redox enzyme, phosphatase. Based on intracellular localization, 52 proteins were divided into extracellular proteins, inner proteins, the ribonucleoprotein complex proteins including inner proteins to most, followed by the ribonucleoprotein complex. According to the signaling network diagram, all the differentially expressed proteins in three complex network area and four relatively simple network area. Conclusions： Chemotherapy sensitivity of large B cell lymphoma involved changes of many proteins and a plurality of signal pathway, among there are have complex relations.