Two-dimensional difference gel electrophoresis to reveal proteins in plasma associated with high risk prostate cancer

• Prostate cancer is a common but highly variable disease. Conventional methods for prognostication are limited and needed to be complemented by novel biomarkers which could identify clinically significant tumors at a curable timepoint. With the aim to find biomarkers in plasma for high risk prostate cancer, we combined the ProteoMiner technology for protein fractionation with 2-dimentional difference gel electrophoresis (2D-DIGE). Plasma samples from patients with high risk tumors, defined to have bone metastases (M1, N=7) or locally advanced or poorly differentiated prostate cancer (M0, N=14), or benign disease (N=15) were analyzed. As a result of combined univariate and multivariate analyses (orthogonal partial least-squares discriminant analysis, OPLS-DA), 338 protein spots were found to be significantly associated with high risk prostate cancer. Ninety-eight (98) of the spots were successfully identified by LC-MS/MS, and OPLS-DA of those resulted in a reliable method for class separation; M1 vs. M0 vs. B (R2Xcum: 31.1%, R2Y cum: 59.9%, Q2cum: 41.4%, P < 0.0001). The panel of identified potential protein markers for high risk prostate cancer included highly to intermediately abundant plasma proteins involved in key processes such as lipid transport, coagulation, inflammation, and immune responses. Their putative roles for prostate cancer progression are discussed.

Nyckelord

biomarkers

2D-DIGE

plasma

prostate cancer

proteomics

PorteoMiner

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)