Proteomic-based approach for biomarkers discovery in early detection of invasive urothelial carcinoma.

Identification of reliable non-invasive markers for the detection of invasive phenotype of urothelial carcinoma is needed. This study characterizes and compares protein expression profiles of adjacent non-neoplastic urothelium and invasive urothelial carcinoma to identify biomarkers for early detection of de novo bladder cancer. Differences in protein expression between adjacent non-neoplastic and high-grade, stage T4, grade 3 invasive urothelial carcinoma tissues were investigated using 2-DE, MALDI-TOF-MS, and data processing. Ingenuity Pathway Analysis (IPA) was applied to examine the biological mechanisms represented by the altered proteins. The 2-DE of the adjacent non-neoplastic urothelium and invasive urothelial carcinoma showed reproducibly similar proteomic mapping for each group distinguishing adjacent non-neoplastic urothelium from invasive urothelial carcinoma. Twenty-one proteins were altered in expression and one of these proteins, Choroideremia-like protein (CHML) was significantly overexpressed (p<0.005) and therefore was analyzed further using IHC and Western blot. Urothelial carcinoma presented an elevated expression of CHML but not adjacent non-neoplastic or normal bladder tissues. IPA revealed the involvement of CHML in cell morphology, cellular assembly, and organization. Further investigation is warranted to elucidate the biological significance of CHML and to validate its role as a biomarker for early detection of invasive urothelial carcinoma de novo.