Abstract
BackgroundTo 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.ResultsWe 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.ConclusionsBased 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.
Highlights
Despite recent advances in surgical techniques, perioperative chemo radiotherapy and the development of molecularly targeted therapies, muscle-invasive bladder transitional cell carcinoma (BTCC) is still a major epidemiological problem whose incidence continues to rise each year [1]
Discovery of proteome expression profile that are integral to neoplastic cells specialized stroma may advance our understanding of the cancer biology and yield novel biomarkers and targets for anticancer therapies
Identification of the proteins We respectively identified 998, 991, 957, 1086 proteins from the 4 cancer stromal samples
Summary
Despite recent advances in surgical techniques, perioperative chemo radiotherapy and the development of molecularly targeted therapies, muscle-invasive bladder transitional cell carcinoma (BTCC) is still a major epidemiological problem whose incidence continues to rise each year [1]. Though some molecular pathogenesis studies on invasive bladder carcinoma have been undertaken successfully on the gene and transcription levels, the carcinogenic mechanism remains to be elucidated. In this regard, using stroma as a sample. As one of the solid tumors, muscle-invasive BTCC are composed of two independent while interactive components: the neoplastic epithelial cells and the surrounding cancer stroma. These two components interactive and in charge of the cancer biology as a functional whole. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature
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