scholarly journals Multi-omics biomarker pipeline reveals elevated levels of protein-glutamine gamma-glutamyltransferase 4 in seminal plasma of prostate cancer patients

2017 ◽  
Author(s):  
Andrei P. Drabovich ◽  
Punit Saraon ◽  
Mikalai Drabovich ◽  
Theano D. Karakosta ◽  
Apostolos Dimitromanolakis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Blood Serum ◽  
Cancer Patients ◽  
Seminal Plasma ◽  
Biomarker Discovery ◽  
Prognostic Significance ◽  
Specific Antigen ◽  
Low Grade ◽  
Gamma Glutamyltransferase ◽  
Negative Biopsy

AbstractPurposeProstate-specific antigen, a blood serum biomarker of prostate cancer, lacks specificity and prognostic significance, so considerable efforts are devoted to developing novel biomarkers. Seminal plasma, due to its proximity to prostate, is a promising fluid for biomarker discovery and non-invasive diagnostics. In this study, we investigated if seminal plasma proteins could increase specificity of detecting primary prostate cancer and discriminate between high- and low-grade cancers.Experimental DesignTo select 148 most promising biomarker candidates, we combined proteins identified through five independent data mining or experimental approaches: tissue transcriptomics, seminal plasma proteomics, cell secretomics, tissue specificity and androgen regulation. A rigorous biomarker development pipeline based on targeted proteomics assays was designed to evaluate the most promising candidates.ResultsWe qualified 77 and verified 19 proteins in seminal plasma of 67 negative biopsy and 155 prostate cancer patients. Verification revealed a prostate-specific, secreted and androgen-regulated protein-glutamine gamma-glutamyltransferase 4 (TGM4), which could predict prostate cancer on biopsy and outperformed age and serum PSA. Machine-learning approaches also revealed improved multi-marker combinations for diagnosis and prognosis. In the independent verification set measured by an inhouse ELISA, TGM4 was up-regulated 3.7-fold (P=0.006) and revealed AUC 0.66 for detecting prostate cancer on biopsy for patients with serum PSA≥4 ng/mL and age≥50. Low levels of TGM4 (median 120 pg/mL) were detected in blood serum, but could not differentiate between negative biopsy, prostate cancer or prostate inflammation.ConclusionsPerformance of TGM4 warrants its further investigation within the distinct genomic subtypes and evaluation for the inclusion into emerging multi-biomarker panels.

Prognostic Significance of Disseminated Tumor Cells in the Bone Marrow of Prostate Cancer Patients Treated With Neoadjuvant Hormone Treatment

2008 ◽  
Vol 26 (30) ◽  
pp. 4928-4933 ◽  
Author(s):  
Jens Köllermann ◽  
Steffen Weikert ◽  
Martin Schostak ◽  
Carsten Kempkensteffen ◽  
Klaus Kleinschmidt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Radical Prostatectomy ◽  
Hormone Therapy ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Specific Antigen ◽  
Disseminated Tumor Cells ◽  
Significant Prognostic Factor

Purpose To explore whether the presence of occult disseminated tumor cells (DTCs) in the bone marrow before neoadjuvant hormone therapy influences the prognosis of patients with organ confined prostate cancer treated by radical prostatectomy. Patients and Methods Pretreatment bone marrow aspirates from 193 cT (1-4) pN0M0 prostate cancer patients submitted to neoadjuvant hormone therapy (mean, 8 months) followed by radical prostatectomy were immunohistochemically evaluated by anticytokeratin antibody A45-B/B3 previously validated for the detection of DTCs. Bone marrow status was compared with established clinical and histopathologic risk parameters. Patients’ outcome was evaluated using prostate-specific antigen (PSA) blood serum measurements as surrogate marker for recurrence over a median follow-up of 44 months. Results DTCs were detected in 44.6% of patients. Bone marrow status neither correlated with tumor grade and stage, nor with the pretreatment PSA risk category (all P values > .05). In the univariate Kaplan-Meier analysis, the presence of DTCs was a significant prognostic factor with respect to poor PSA progression-free survival (log-rank test P = .0035). Using a multivariable piecewise Cox regression model, the presence of DTCs was an independent predictor of PSA relapse (relative risk 1.82; P = .014). Conclusion The presence of DTCs in the bone marrow of patients with prostate cancer before neoadjuvant hormone therapy and subsequent surgery represents an independent prognostic parameter, suggesting that DTCs may contribute to the failure of current neoadjuvant hormone therapy regimens.

Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease

2005 ◽  
Vol 12 (1) ◽  
pp. 109-117 ◽  
Author(s):  
A Berruti ◽  
A Mosca ◽  
M Tucci ◽  
C Terrone ◽  
M Torta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Chromogranin A ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Specific Antigen ◽  
Serum Lactate Dehydrogenase ◽  
Refractory Disease ◽  
Prognostic Role ◽  
Hormone Refractory

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0–141.0) U/l at baseline, 19.1 (3.0–486.0) U/l after 3 months, 20.8 (3.0–702.0) U/l after 6 months and 39.4 (3.0–414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.

scholarly journals Multi-omics Biomarker Pipeline Reveals Elevated Levels of Protein-glutamine Gamma-glutamyltransferase 4 in Seminal Plasma of Prostate Cancer Patients

2019 ◽  
Vol 18 (9) ◽  
pp. 1807-1823 ◽  
Author(s):  
Andrei P. Drabovich ◽  
Punit Saraon ◽  
Mikalai Drabovich ◽  
Theano D. Karakosta ◽  
Apostolos Dimitromanolakis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Seminal Plasma ◽  
Gamma Glutamyltransferase

scholarly journals Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: a prospective, multicenter study in biopsy-naïve men

2021 ◽  
Author(s):  
Rianne J. Hendriks ◽  
Marloes M. G. van der Leest ◽  
Bas Israël ◽  
Gerjon Hannink ◽  
Anglita YantiSetiasti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Stratification ◽  
Specific Antigen ◽  
Low Grade ◽  
Diagnostic Study ◽  
High Grade ◽  
Net Benefit ◽  
Conditional Strategy ◽  
Detection Rates ◽  
Guided Biopsy

Abstract Background Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of “unnecessary” prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. Methods This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥−2.8. Decision curve analysis (DCA) was performed to assess clinical utility. Results Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. Conclusions SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

Detectable Prostate Specific Antigen Between 60 and 120 Days Following Radical Prostatectomy for Prostate Cancer: Natural History and Prognostic Significance

2006 ◽  
Vol 176 (2) ◽  
pp. 559-563 ◽  
Author(s):  
Shomik Sengupta ◽  
Carl M. Christensen ◽  
Horst Zincke ◽  
Jeffrey M. Slezak ◽  
Bradley C. Leibovich ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Natural History ◽  
Prostate Specific Antigen ◽  
Prognostic Significance ◽  
Specific Antigen
Sign in / Sign up

Export Citation Format

Share Document