Abstract
Prostate cancer (PCa) is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24) compared to benign (n = 21) prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies.
Highlights
Prostate cancer (PCa) is currently the leading cancer among men in western countries [1]
We investigated the comparative proteome of prostate cancer and its adjacent histological benign tissue from cancer patients with definitive pathological characterization in our 2-D differential in-gel electrophoresis (DIGE) system for protein 2D electrophoresis [13] and MALDI-TOF-MS/MS for protein identification
2D-DIGE Analysis and mass spectrometry In this study, we were able to establish a standard procedure for manual micro dissection of radical prostatectomy samples to obtain pathologically evaluated tumor and benign tissues for proteome analysis
Summary
Prostate cancer (PCa) is currently the leading cancer among men in western countries [1]. Protein expression analysis of patient materials are informative led to the identifying cancer specific markers for diagnosis, therapeutic targets and is the basis for revealing various cellular events associated with cancer progression [7]. Several research groups have already performed protein and gene expression profiling studies on surgical and biopsy PCa specimens [8,9,10,11,12] but most of the potential reported markers are not in clinical application for definitive diagnosis of PCa. previous studies focussed on interindividual comparisons of proteomic analysis of radical prostatectomies from cancer patients to those of non cancer patients with conventional 2DE. Intraindividual analysis of tumor and benign tissue samples (adjacent to tumor) from the same cancer patients may reduce technical variability and provide a means to increase specificity of the results and to increase chances to identify specific disease-associated protein alterations
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