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A Novel Quantitative Multiplex Tissue Immunoblotting for Biomarkers Predicts a Prostate Cancer Aggressive Phenotype.

ABSTRACT: 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.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 ?m sections. Multivariate logistic regression (MLR) was applied to model our 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.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.Comprehensive profiling of biomarkers using MTI predicts prostate cancer aggressive phenotype in RP and AS biopsies.

SUBMITTER: Zhu G

PROVIDER: S-EPMC4755280 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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A Novel Quantitative Multiplex Tissue Immunoblotting for Biomarkers Predicts a Prostate Cancer Aggressive Phenotype.

Zhu Guangjing G Liu Zhi Z Epstein Jonathan I JI Davis Christine C Christudass Christhunesa S CS Carter H Ballentine HB Landis Patricia P Zhang Hui H Chung Joon-Yong JY Hewitt Stephen M SM Miller M Craig MC Veltri Robert W RW

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20150924 12

<h4>Background</h4>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.<h4>Methods</h4>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 tissu ...[more]

PMID: 26404961

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Project description:PURPOSE: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. MATERIALS AND METHODS: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. RESULTS: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ?8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ?8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. CONCLUSION: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an "active surveillance" strategy.

Dataset Information

A Novel Quantitative Multiplex Tissue Immunoblotting for Biomarkers Predicts a Prostate Cancer Aggressive Phenotype.

Publications

A Novel Quantitative Multiplex Tissue Immunoblotting for Biomarkers Predicts a Prostate Cancer Aggressive Phenotype.

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