title: A Novel Quantitative Multiplex Tissue Immunoblotting for Biomarkers Predicts a Prostate Cancer Aggressive Phenotype.
abstract: BACKGROUND
  Early prediction of disease progression in men with very low-risk (VLR) prostate cancer who selected active surveillance (AS) rather than immediate treatment could reduce morbidity associated with overtreatment.
  
  
  METHODS
  We evaluated the association of six biomarkers [Periostin, (-5, -7) proPSA, CACNA1D, HER2/neu, EZH2, and Ki-67] with different Gleason scores and biochemical recurrence (BCR) on prostate cancer TMAs of 80 radical prostatectomy (RP) cases. Multiplex tissue immunoblotting (MTI) was used to assess these biomarkers in cancer and adjacent benign areas of 5 μm sections. Multivariate logistic regression (MLR) was applied to model our results.
  
  
  RESULTS
  In the RP cases, CACNA1D, HER2/neu, and Periostin expression were significantly correlated with aggressive phenotype in cancer areas. An MLR model in the cancer area yielded a ROC-AUC = 0.98, whereas in cancer-adjacent benign areas, yielded a ROC-AUC = 0.94. CACNA1D and HER2/neu expression combined with Gleason score in a MLR model yielded a ROC-AUC = 0.79 for BCR prediction. In the small biopsies from an AS cohort of 61 VLR cases, an MLR model for prediction of progressors at diagnosis retained (-5, -7) proPSA and CACNA1D, yielding a ROC-AUC of 0.78, which was improved to 0.82 after adding tPSA into the model.
  
  
  CONCLUSIONS
  The molecular profile of biomarkers is capable of accurately predicting aggressive prostate cancer on retrospective RP cases and identifying potential aggressive prostate cancer requiring immediate treatment on the AS diagnostic biopsy but limited in BCR prediction.
  
  
  CONCLUSIONS
  Comprehensive profiling of biomarkers using MTI predicts prostate cancer aggressive phenotype in RP and AS biopsies.
authors.affiliation: The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Guangjing
authors.initials: G
authors.lastname: Zhu
authors.affiliation: The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.affiliation: The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Christine
authors.initials: C
authors.lastname: Davis
authors.affiliation: The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Christhunesa S
authors.initials: CS
authors.lastname: Christudass
authors.affiliation: The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: H Ballentine
authors.initials: HB
authors.lastname: Carter
authors.affiliation: The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Landis
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Joon-Yong
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.affiliation: Statistical Consultant, Lindale, Texas.
authors.forename: M Craig
authors.initials: MC
authors.lastname: Miller
authors.affiliation: The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland. rveltri1@jhmi.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Veltri
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor