Research On Stromal Proteome Expression Profile And Muscle-invasive Bladder Cancer

Objectives:To globally characterize the cancer stroma expression profile of muscle-invasive bladder transitional cell carcinoma and to discuss the cancer biology as well as biomarker discovery from stroma.Methods:Highly purify muscle-invasive bladder transitional cell carcinoma and n ormal stroma by laser capture microdissection (LCM); Separation of peptide mixtur e by two-dimensional liquid chromatography (2D-LC) followed by electrospray ioni zation-tandem mass spectrometry (ESI-MS/MS) identification; Bioinformatics analysi s of the identified proteins; GO biological process analysis; Pathway analysis in di fferently expressed proteins; Evidence based biomarker exploration.Results:We identified868/872commonly expressed proteins and978differential proteins from4paired cancer and normal stromal samples.487/491proteins specific expressed in cancer/normal stroma. Differential proteins were compared with the entire list of the international protein index (IPI), and there were42/42gene ontology (GO) terms exhibited as enriched and8/5exhibited 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.Conclusions:These observations promise new biomarkers of prognosis and a new compartment to target therapy. Furthermore, it is now well accepted that the cancer and its stroma have a bidirectional relationship at multiple levels to elicit carcinogenesis, invasion, and progression. As one of the solid tumor, we can imagine that stromal cells plays a critical role in muscle-invasive BTCC based on substantial evidences, though there has been no report of large-scale proteomics study on the muscle-invasive BTCC stroma.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.