title: MALDI-MS tissue imaging identification of biliverdin reductase B overexpression in prostate cancer.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Analytical Chemistry and Radiochemistry, CCB - Center for Chemistry and Biomedicine, Leopold-Franzens University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria; Institute of Legal Medicine, Innsbruck Medical University, Muellerstraße 44, 6020 Innsbruck, Austria.
authors: Johannes Dominikus
authors: JD
authors: Pallua
authors: Georg
authors: G
authors: Schaefer
authors: Christof
authors: C
authors: Seifarth
authors: Michael
authors: M
authors: Becker
authors: Stephan
authors: S
authors: Meding
authors: Sandra
authors: S
authors: Rauser
authors: Axel
authors: A
authors: Walch
authors: Michael
authors: M
authors: Handler
authors: Michael
authors: M
authors: Netzer
authors: Marina
authors: M
authors: Popovscaia
authors: Melanie
authors: M
authors: Osl
authors: Christian
authors: C
authors: Baumgartner
authors: Herbert
authors: H
authors: Lindner
authors: Leopold
authors: L
authors: Kremser
authors: Bettina
authors: B
authors: Sarg
authors: Georg
authors: G
authors: Bartsch
authors: Christian W
authors: CW
authors: Huck
authors: Günther K
authors: GK
authors: Bonn
authors: Helmut
authors: H
authors: Klocker
mesh_terms: D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006418:Heme / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D006418:Heme; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase
keywords: AMACR; BLVR; Biliverdin reductase; GS; Gleason score (sum of the two most abundant tumor Gleason patterns); HE; Heme metabolism; IHC; Mass spectrometry tissue imaging; P53-related protein P63; P63; PCa; PSA; Prostate cancer; ROI; TMA; Tissue biomarker; alpha methylacyl CoA racemase; biliverdin reductase; hematoxilin-eosine; immunohistochemistry; pT; pathological tumor stage; prostate cancer; prostate specific antigen; region of interest; tissue micro array.