Heterogeneity research in muscle-invasive bladder cancer based on differential protein expression analysis
Heterogeneity research in muscle-invasive bladder cancer based on differential protein expression analysis
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基于差异蛋白表达分析的肌层浸润性膀胱癌异质性研究
DOI：
10.1007/s12032-014-0021-9
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发表时间：
2014-09-01
期刊：
影响因子：
3.4
通讯作者：
Niu, Hai Tao
中科院分区：
文献类型：
--
作者：
Liu, Peng Fei;Cao, Yan Wei;Niu, Hai Tao
本研究的目的是研究不同风险组肌肉浸润性膀胱癌(MIBC)细胞的表达谱，探讨生物通路改变在MIBC细胞异质性中的关键作用。30个个体样本(癌和非癌标本)取自MIBC患者。采用激光捕获显微切割法获取均一的MIBC细胞和正常尿路上皮细胞。用iTRAQ和2D-LC-MS/MS对差异表达的蛋白质进行定量和鉴定。然后，用ArrayTrack™软件对差异显著的蛋白质进行进一步分析。将感兴趣的蛋白质与已发表的文献进行比较，讨论其确切的功能。在这项研究中，共鉴定出3,073个非冗余蛋白；因此，855/2,210/633(相对于正常组的倍数变化>；1.5)分别出现在高/中/低风险组中。从ArrayTrack™软件输出的瑞士ACC617/1,620/463蛋白分别出现在高、中、低风险组中。通路分析显示，遗传信息处理类别中主要改变的通路(TOP-10，p<；(0.05))在高危和中危人群中相似，包括京都基因和基因组百科全书(KEGG)剪接体、蛋白质输出、核糖体通路。高危组主要代谢途径包括糖酵解/糖异生、戊糖磷酸、丙酮酸代谢途径，中危组主要包括谷胱甘肽代谢、柠檬酸循环、氧化磷酸化途径。低危组主要改变的途径包括局灶性黏附途径和ECM-受体相互作用途径。这些改变的生物学途径与MIBC异质性的调节密切相关。遗传信息处理类和代谢类(无氧或有氧)的KEGG通路在决定MIBC细胞的恶性表型中起着至关重要的作用。蛋白质定量分析与KEGG通路分析相结合，有助于筛选候选生物标志物，指导MIBC的生物分子治疗。
The aim of this study was to study the expression profiles of muscle-invasive bladder cancer (MIBC) cells of different risk groups and to explore the crucial role of biological pathway change in heterogeneity of MIBC cells. Thirty individual samples (cancer and non-cancerous specimens) were obtained from patients with MIBC. Laser capture microdissection was employed to harvest the homogeneous MIBC cells and normal urothelial cells. iTRAQ and 2D-LC–MS/MS were used to quantify and identify the differently expressed proteins. Then, the significantly changed proteins were further analyzed using Arraytrack ™ software. The interested proteins were compared with the published literatures to discuss the exact functions. A total of 3,073 non-redundant proteins were identified in this research; therefore, 855/2,210/633 (fold change >1.5 relative to normal group) presented in high-/median-/low-risk groups, respectively. 617/1,620/463 proteins with SWISS-ACC number output from Arraytrack ™ software and presented in high-/median-/low-risk groups, respectively. Pathway analysis revealed that the mainly changed pathways (top-10,p< 0.05) inGenetic information processingcategory were similar in high- and median-risk groups, including Kyoto Encyclopedia of Genes and Genomes (KEGG) spliceosome, protein export, ribosome pathways. The mainly altered pathways inMetabolismcategory included glycolysis/gluconeogenesis, pentose phosphate, pyruvate metabolism pathway for high-risk group, and glutathione metabolism, citrate cycle, oxidative phosphorylation pathways for median-risk group. The major changed pathways for low-risk group included focal adhesion pathway and ECM-receptor interaction pathway. The changed biological pathways are closely related to the regulation of heterogeneity for MIBC. The KEGG pathways ofGenetic information processingcategory andMetabolism(anaerobic or aerobic) category play a crucial role in determining the malignant phenotype of MIBC cells. The quantification analysis of proteins combining with the KEGG pathway analysis contributes to screening candidate biomarkers and guides the biological molecular therapy of MIBC.