Utility of RhoC and ZAG protein expression as biomarkers for prediction of pSa failure following radical prostatectomy for high grade prostate cancer

Mills, John; Oliver, Alice; Sherwin, Justin C; Frydenberg, Mark; Peters, Justin; Costello, Anthony J.; Harewood, Laurence; Love, Christopher G.; Redgrave, Nicholas; Golen, Kenneth L. van; Bailey, Michael; Pedersen, John

doi:10.1097/pat.0b013e3283581780

Cited by 5 publications

(6 citation statements)

References 27 publications

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“…High risk cancers generally had higher serum PSA concentrations, higher proportions of cores with cancer, higher median cancer length per core, and more adverse Gleason variables than not high-risk cancers ( Table 2). MUC1 expression was more frequent and ZAG staining less frequent in the biopsies from high-risk cancers compared with those not high-risk, consistent with the known biology of these proteins in prostate cancer [10,12,[30][31][32][33]. In those biopsies with >40% MUC1 staining, the associated RPx specimens had a much higher percentage of pattern 4 histopathology than in those without biopsy MUC1 expression (median 70% versus 20%, p<0.001, Wilcoxon rank-sum test).…”

Section: Resultssupporting

confidence: 58%

“…Prior studies of RPx tissue have shown positive MUC1 or ZAG expression to be predictive of PSA failure and/or metastases, [10,12,[30][31][32][33] but no studies have investigated these markers in prostate biopsies, although Gunia et al showed that MUC1 expression in transurethral resection specimens ("incidental prostate cancers") predicted adverse pathology following subsequent radical prostatectomy [41]. The failure of our study to document a predictive capacity of MUC1 expression is most likely related to the small sample size (as relatively few biopsies stained MUC1 positive, the study lacked power to assess this biomarker), although it is also possible that its expression in biopsies is not strongly related to RPx pathology.…”

Section: Discussionmentioning

confidence: 99%

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Assessing Expression of MUC1 and ZAG Protein Biomarkers in Prostate Biopsies Improves Prediction of Adverse Pathology Following Radical Prostatectomy

Durrani¹,

Waldron²,

Cherry³

et al. 2015

TOPCANJ

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Abstract:Objectives: To determine whether assessing expression of MUC1 and ZAG proteins in prostate biopsies, by immunohistochemistry, improves prediction of radical prostatectomy histopathology, which in turn predicts longer-term outcomes. Methods:We studied 231 consecutive patients managed by two experienced urologic surgeons (MF, LH). Each patient had prostate biopsies revealing cancer followed by a radical prostatectomy. Expression of MUC1 and ZAG in biopsy tissue was assessed by immunohistochemistry, masked to the radical prostatectomy histopathology. Data were analysed by Chi-square, Fischer exact test & Mann Whitney U test followed by multivariate analysis using binary logistic regression.Results: By univariate analysis, MUC1 expression in prostate biopsies was associated with worse histopathology in the radical prostatectomy specimen (p<0.023), while ZAG expression was associated with better pathology (p=0.03). By multivariate analysis decreased expression of ZAG in biopsies (p=0.02), but not MUC1 expression, improved prediction of high-risk radical prostatectomy pathology beyond conventional biopsy variables; neither MUC1 nor ZAG staining improved prediction of minimal-risk cancers.Conclusions: Assessment of ZAG expression in prostate biopsies, and possibly MUC1 expression, may improve knowledge of prostate cancers in vivo or after radical prostatectomy.

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Section: Resultssupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Assessing Expression of MUC1 and ZAG Protein Biomarkers in Prostate Biopsies Improves Prediction of Adverse Pathology Following Radical Prostatectomy

Durrani¹,

Waldron²,

Cherry³

et al. 2015

TOPCANJ

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“…A down expression of the ZA2G was observed in the tissue of patients affected by hepatocellular carcinoma (HCC) [ 37 ] and it was associated with a poor overall survival, worst disease-free survival, relapse-free survival and distant metastatic progression-free survival. Moreover, ZA2G protein was also found to be lower in 57 patients with a rising of prostate specific antigen after surgery and not in the other 32 patients [ 38 ]. ZAG expression was inversely correlated with Gleason pattern and correlated with a favourable outcome.…”

Section: Discussionmentioning

confidence: 99%

Tumor size, stage and grade alterations of urinary peptidome in RCC

et al. 2015

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BackgroundSeveral promising biomarkers have been found for RCC, but none of them has been used in clinical practice for predicting tumour progression. The most widely used features for predicting tumour aggressiveness still remain the cancer stage, size and grade. Therefore, the aim of our study is to investigate the urinary peptidome to search and identify peptides whose concentrations in urine are linked to tumour growth measure and clinical data.MethodsA proteomic approach applied to ccRCC urinary peptidome (n = 117) based on prefractionation with activated magnetic beads followed by MALDI-TOF profiling was used. A systematic correlation study was performed on urinary peptide profiles obtained from MS analysis. Peptide identity was obtained by LC–ESI–MS/MS.ResultsFifteen, twenty-six and five peptides showed a statistically significant alteration of their urinary concentration according to tumour size, pT and grade, respectively. Furthermore, 15 and 9 signals were observed to have urinary levels statistically modified in patients at different pT or grade values, even at very early stages. Among them, C1RL, A1AGx, ZAG2G, PGBM, MMP23, GP162, ADA19, G3P, RSPH3, DREB, NOTC2 SAFB2 and CC168 were identified.ConclusionsWe identified several peptides whose urinary abundance varied according to tumour size, stage and grade. Among them, several play a possible role in tumorigenesis, progression and aggressiveness. These results could be a useful starting point for future studies aimed at verifying their possible use in the managements of RCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0693-8) contains supplementary material, which is available to authorized users.

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“…We have previously demonstrated that loss of expression of zinc‐alpha 2‐glycoprotein (AZGP1 or ZAG) protein expression by immunohistochemistry is associated with an increased risk of recurrence after radical prostatectomy . This finding has been validated in several later studies, and loss of AZGP1 expression has also been shown to predict subsequent development of metastatic disease and death from prostate cancer . In addition, loss of transcriptional expression of AZGP1 has been associated with prostate cancer recurrence and death and is 1 of 12 prognostic transcripts measured in a commercially available tissue‐based test called OncotypeDX from Genomic Health .…”

Section: Introductionmentioning

confidence: 93%

Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort

et al. 2016

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Background Given the uncertainties inherent in clinical measures of prostate cancer aggressiveness, clinically validated tissue biomarkers are needed. We tested whether Alpha-2-Glycoprotein 1, Zinc-Binding (AZGP1) protein levels, measured by immunohistochemistry, and RNA expression, by RNA in situ hybridization (RISH), predict recurrence after radical prostatectomy independent of clinical and pathological parameters. Methods AZGP1 IHC and RISH were performed on a large multi-institutional tissue microarray resource including 1275 men with 5 year median follow-up. The relationship between IHC and RISH expression levels was assessed using the Kappa analysis. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazards models and the Log-rank test. Results Absent or weak expression of AZGP1 protein was associated with worse recurrence free survival (RFS), disease specific survival and overall survival after radical prostatectomy in univariable analysis. AZGP1 protein expression, along with pre-operative serum PSA levels, surgical margin status, seminal vesicle invasion, extracapsular extension and Gleason score predicted RFS on multivariable analysis. Similarly, absent or low AZGP1 RNA expression by RISH predicted worse RFS after prostatectomy in univariable and multivariable analysis. Conclusions In our large, rigorously designed validation cohort, loss of AZGP1 expression predicts RFS after radical prostatectomy independent of clinical and pathological variables.

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Utility of RhoC and ZAG protein expression as biomarkers for prediction of pSa failure following radical prostatectomy for high grade prostate cancer

Cited by 5 publications

References 27 publications

Assessing Expression of MUC1 and ZAG Protein Biomarkers in Prostate Biopsies Improves Prediction of Adverse Pathology Following Radical Prostatectomy

Assessing Expression of MUC1 and ZAG Protein Biomarkers in Prostate Biopsies Improves Prediction of Adverse Pathology Following Radical Prostatectomy

Tumor size, stage and grade alterations of urinary peptidome in RCC

Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort

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