A novel quantitative multiplex tissue immunoblotting for biomarkers predicts a prostate cancer aggressive phenotype

Guangjing Zhu, Zhi Liu, Jonathan I. Epstein, Christine Davis, Christhunesa S. Christudass, H. Ballentine Carter, Patricia Landis, Hui Zhang, Joon Yong Chung, Stephen M. Hewitt, M. Craig Miller, Robert W. Veltri

Research output: Contribution to journalArticle

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 mm 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. Impact: Comprehensive profiling of biomarkers using MTI predicts prostate cancer aggressive phenotype in RP and AS biopsies. Cancer Epidemiol Biomarkers Prev; 24(12); 1864-72.

Original languageEnglish (US)
Pages (from-to)1864-1872
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume24
Issue number12
DOIs
StatePublished - Dec 2015

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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