Department of Urology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, China.
Department of Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, China.
Cancer Cell Int. 2012 Aug 25;12(1):39. doi: 10.1186/1475-2867-12-39.
To globally characterize the cancer stroma expression profile of muscle-invasive transitional cell carcinoma and to discuss the cancer biology as well as biomarker discovery from stroma. Laser capture micro dissection was used to harvest purified muscle-invasive bladder cancer stromal cells and normal urothelial stromal cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature.
We identified 868/872 commonly expressed proteins and 978 differential proteins from 4 paired cancer and normal stromal samples using laser capture micro dissection coupled with two-dimensional liquid chromatography tandem mass spectrometry. 487/491 proteins uniquely expressed in cancer/normal stroma. Differential proteins were compared with the entire list of the international protein index (IPI), and there were 42/42 gene ontology (GO) terms exhibited as enriched and 8/5 exhibited as depleted in cellular Component, respectively. Significantly altered pathways between cancer/normal stroma mainly include metabolic pathways, ribosome, focal adhesion, etc. Finally, descriptive statistics show that the stromal proteins with extremes of PI and MW have the same probability to be a biomarker.
Based on our results, stromal cells are essential component of the cancer, biomarker discovery and network based multi target therapy should consider neoplastic cells itself and corresponding stroma as whole one.
对肌层浸润性移行细胞癌的肿瘤基质表达谱进行全球特征分析,并探讨肿瘤生物学以及从基质中发现生物标志物。采用激光捕获显微切割技术从 4 对样本中分离纯化肌层浸润性膀胱癌基质细胞和正常尿路上皮基质细胞。采用二维液相色谱串联质谱技术鉴定蛋白质组表达谱。使用生物信息学工具对差异蛋白进行进一步分析,并与已发表的文献进行比较。
我们使用激光捕获显微切割结合二维液相色谱串联质谱技术,从 4 对配对的癌症和正常基质样本中鉴定出 868/872 个共同表达蛋白和 978 个差异蛋白。487/491 个蛋白在癌症/正常基质中特异表达。将差异蛋白与国际蛋白质索引(IPI)的全部列表进行比较,有 42/42 个基因本体(GO)术语在细胞成分中表现为富集,8/5 个表现为缺失。癌症/正常基质之间差异明显的通路主要包括代谢途径、核糖体、焦点黏附等。最后,描述性统计显示,PI 和 MW 极端的基质蛋白成为生物标志物的可能性相同。
基于我们的结果,基质细胞是肿瘤的重要组成部分,生物标志物的发现和基于网络的多靶点治疗应将肿瘤细胞本身和相应的基质作为一个整体来考虑。