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MALDI-MS tissue imaging identification of biliverdin reductase B overexpression in prostate cancer.
J. Proteomics 91, 500-514 (2013)
[object Object]: New biomarkers are needed to improve the specificity of prostate cancer detection and characterisation of individual tumors. In a proteomics profiling approach using MALDI-MS tissue imaging on frozen tissue sections, we identified discriminating masses. Imaging analysis of cancer, non-malignant benign epithelium and stromal areas of 15 prostatectomy specimens in a test and 10 in a validation set identified characteristic m/z peaks for each tissue type, e.g. m/z 10775 for benign epithelial, m/z 6284 and m/z 6657.5 for cancer and m/z 4965 for stromal tissue. A 10-fold cross-validation analysis showed highest discriminatory ability to separate tissue types for m/z 6284 and m/z 6657.5, both overexpressed in cancer, and a multicomponent mass peak cluster at m/z 10775-10797.4 overexpressed in benign epithelial tissue. ROC AUC values for these three masses ranged from 0.85 to 0.95 in the discrimination of malignant and non-malignant tissue. To identify the underlying proteins, prostate whole tissue extract was separated by nano-HPLC and subjected to MALDI TOF/TOF analysis. Proteins in fractions containing discriminatory m/z masses were identified by MS/MS analysis and candidate marker proteins subsequently validated by immunohistochemistry (IHC). Biliverdin reductase B (BLVRB) turned out to be overexpressed in PCa tissue. BIOLOGICAL SIGNIFICANCE: In this study on cryosections of radical prostatectomies of prostate cancer patients, we performed a MALDI-MS tissue imaging analysis and a consecutive protein identification of significant m/z masses by nano-HPLC, MALDI TOF/TOF and MS/MS analysis. We identified BLVRB as a potential biomarker in the discrimination of PCa and benign tissue, also suggesting BVR as a feasible therapeutic target.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Mass spectronomy tissue imaging; Prostate cancer; Tissue biomarker; Biliverdin reductase; Heme metabolism; Major Physiological Cytoprotectant ; Ix-beta Reductase ; Mass-spectrometry ; Biomarker Discovery ; Hepatocellular-carcinoma ; Oxidative Stress ; Heme Oxygenase-1 ; Protein Markers ; Ovarian-cancer ; Breast-cancer
ISSN (print) / ISBN 1874-3919
Journal Journal of Proteomics
Quellenangaben Volume: 91, Issue: 8, Pages: 500-514
Reviewing status Peer reviewed