Purpose: To globally characterize the stroma expression profile of superficial bladder transitional cell carcinoma and to discuss the cancer biology as well as biomarker discovery from stromal cells.
Methods: Laser capture microdissection was used to harvest purified bladder cancer stromal cells and normal stromal cells from 4 paired samples. Next, 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.
Results: A total of 606/601 proteins commonly appeared in 4 paired samples. Six hundred and thirty-seven proteins were differentially expressed between cancer and normal stroma. Among them, 321/316 proteins specific expressed in cancer/normal stromal cells. Differential proteins were compared with the entire list of the international protein index (IPI). 36/49 GO terms exhibited as enriched and 25/14 exhibited as depleted in biological process; 39/40 GO terms exhibited as enriched and 9/4 exhibited as depleted in cellular component, respectively. Significantly altered pathways between cancer/normal stroma mainly include focal adhesion, EHEC, oxidative phosphorylation, glycolysis/gluconeogenesis, TCA cycle. Finally, descriptive statistics show the data that PI ≤ 8 have normal distribution and the proteins with extremes of PI and MW have the same probability to be a biomarker.
Conclusions: The present study identified the proteome expression profile of bladder cancer stromal cells and normal stromal cells. Furthermore, our results confirm proteins origin from stroma play important role in cancer biology and highlight a novel view of cancer and stress the importance of including factors related to the cancer stroma into biomarker discovery.