scholarly journals Biofluid quantification of TWEAK/Fn14 axis in combination with a selected biomarker panel improves assessment of prostate cancer aggressiveness

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Xavier Ruiz-Plazas ◽  
Esther Rodríguez-Gallego ◽  
Marta Alves ◽  
Antonio Altuna-Coy ◽  
Javier Lozano-Bartolomé ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Biochemistry ◽  
Specific Antigen ◽  
Total Serum ◽  
Mrna Levels ◽  
Biomarker Panel ◽  
Non Invasive ◽  
Clinical Biomarkers ◽  
Cancer Aggressiveness ◽  
Aggressive Tumors

Abstract Background Conventional clinical biomarkers cannot accurately differentiate indolent from aggressive prostate cancer (PCa). We investigated the usefulness of a biomarker panel measured exclusively in biofluids for assessment of PCa aggressiveness. Methods We collected biofluid samples (plasma/serum/semen/post-prostatic massage urine) from 98 patients that had undergone radical prostatectomy. Clinical biochemistry was performed and several cytokines/chemokines including soluble(s) TWEAK, sFn14, sCD163, sCXCL5 and sCCL7 were quantified by ELISA in selected biofluids. Also, the expression of KLK2, KLK3, Fn14, CD163, CXCR2 and CCR3 was quantified by real-time PCR in semen cell sediment. Univariate, logistic regression, and receiver operating characteristic (ROC) analyses were used to assess the predictive ability of the selected biomarker panel in conjunction with clinical and metabolic variables for the evaluation of PCa aggressiveness. Results Total serum levels of prostate-specific antigen (PSA), semen levels of sTWEAK, fasting glycemia and mRNA levels of Fn14, KLK2, CXCR2 and CCR3 in semen cell sediment constituted a panel of markers that was significantly different between patients with less aggressive tumors [International Society of Urological Pathology (ISUP) grade I and II] and those with more aggressive tumors (ISUP grade III, IV and V). ROC curve analysis showed that this panel could be used to correctly classify tumor aggressiveness in 90.9% of patients. Area under the curve (AUC) analysis revealed that this combination was more accurate [AUC = 0.913 95% confidence interval (CI) 0.782–1] than a classical non-invasive selected clinical panel comprising age, tumor clinical stage (T-classification) and total serum PSA (AUC = 0.721 95% CI 0.613–0.830). Conclusions TWEAK/Fn14 axis in combination with a selected non-invasive biomarker panel, including conventional clinical biochemistry, can improve the predictive power of serum PSA levels and could be used to classify PCa aggressiveness.

scholarly journals A Panel of Urinary Volatile Biomarkers for Differential Diagnosis of Prostate Cancer from Other Urological Cancers

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2017
Author(s):  
Ana Rita Lima ◽  
Joana Pinto ◽  
Carina Carvalho-Maia ◽  
Carmen Jerónimo ◽  
Rui Henrique ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Psa Test ◽  
Biomarker Panel ◽  
Non Invasive ◽  
Detection Tool ◽  
Urological Cancers ◽  
Cancer Types ◽  
Independent Cohort ◽  
New Metabolites

Our group recently developed a urinary 6-biomarker panel for the diagnosis of prostate cancer (PCa) which has a higher level of accuracy compared to the serum prostate specific antigen (PSA) test. Herein, urine from an independent cohort of PCa patients and cancer-free controls was analyzed to further validate the discriminative power of that panel. Additionally, urine from patients diagnosed with bladder cancer (BC) and renal cancer (RC) were included to evaluate the site-specificity of the panel. Results confirmed the ability of the 6-biomarker panel to discriminate PCa patients from controls, but not from other urological cancers. To overcome this limitation, an untargeted approach was performed to unveil discriminant metabolites among the three cancer types. A 10-biomarker panel comprising the original panel plus four new metabolites was established to discriminate PCa from controls, BC, and RC, with 76% sensitivity, 90% specificity, and 92% accuracy. This improved panel also disclosed better accuracy than serum PSA test and provides the basis for a new non-invasive early detection tool for PCa.

scholarly journals Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3373
Author(s):  
Milena Matuszczak ◽  
Jack A. Schalken ◽  
Maciej Salagierski
Keyword(s):  
Prostate Cancer ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Cost Effective ◽  
Non Invasive ◽  
Diagnosis And Prognosis

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

A phase III, randomized, open-label, study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy (NHT) in patients (pts) with metastatic, castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS190-TPS190
Author(s):  
Neeraj Agarwal ◽  
Arun Azad ◽  
Joan Carles ◽  
Simon Chowdhury ◽  
Bradley Alexander McGregor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Soft Tissue ◽  
Objective Response ◽  
Specific Antigen ◽  
Phase Iii ◽  
Disease Stage ◽  
Open Label ◽  
Phase 3 ◽  
Recist 1.1 ◽  
Cancer Aggressiveness

TPS190 Background: Cabozantinib inhibits multiple tyrosine kinases, including MET, VEGFR, RET, and TAM kinases (Tyro3, AXL, MER), involved in tumor growth and angiogenesis, and whose mutations and expression are associated with prostate cancer aggressiveness and poor prognosis. Targeting these kinases with cabozantinib may promote an immune permissive tumor environment and may enhance response to immune checkpoint inhibitors. In the ongoing phase 1b COSMIC-021 study of pts with solid tumors, cabozantinib plus the PD-L1 inhibitor atezolizumab, showed preliminary meaningful clinical activity in soft tissue disease and a tolerable safety profile for 44 pts with mCRPC (Agarwal et al., ASCO 2020; abstract 5564). We present the study design of a phase 3 trial of cabozantinib plus atezolizumab versus second NHT in pts with mCRPC. Methods: This randomized, open-label, controlled phase 3 study (NCT04446117) evaluates the efficacy and safety of cabozantinib plus atezolizumab versus second NHT (abiraterone or enzalutamide) in pts with mCRPC who previously received one NHT to treat metastatic castration-sensitive PC (mCSPC), non-metastatic CRPC (M0 CRPC), or mCRPC. Additional eligibility criteria include histologically or cytologically confirmed adenocarcinoma of the prostate, measurable visceral disease or measurable extrapelvic adenopathy per RECIST 1.1 by investigator, prostate specific antigen progression and/or soft-tissue disease progression, ECOG 0 or 1, and age ≥18 years. Key exclusion criteria include prior nonhormonal therapy for mCRPC and uncontrolled significant illness. Eligible pts (N = 580) are randomized 1:1 to receive cabozantinib (40 mg PO QD) + atezolizumab (1200 mg IV Q3W) vs abiraterone (1000 mg PO QD) + prednisone (5 mg PO BID) or enzalutamide (160 mg PO QD). Designated NHT will differ from previous NHT taken. Randomization is stratified by: liver metastasis (yes, no), prior docetaxel treatment for mCSPC (yes, no), and disease stage for which the first NHT was given (mCSPC, M0 CRPC, mCRPC). Treatment will continue until there is no longer clinical benefit as determined by the treating investigator, unacceptable toxicity, or consent withdrawal. The multiple primary endpoints are progression-free survival per RECIST 1.1 by blinded independent radiology committee (BIRC) and overall survival. Additional endpoints include objective response rate per RECIST 1.1 by BIRC, safety, correlation of biomarkers with outcomes, quality of life and pharmacokinetics. Patient enrollment is ongoing. Clinical trial information: NCT04446117.

The use of Tweak-Fn14 as a non-invasive biomarker panel for prostate cancer

2019 ◽  
Vol 18 (11) ◽  
pp. e3489
Author(s):  
M. Alves Santiago ◽  
X. Ruiz Plazas ◽  
M. Fargas Madriles ◽  
V. Iranzo Aguilar ◽  
E. Rodriguez Gallego ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biomarker Panel ◽  
Non Invasive

Evaluation of the prostate-specific antigen/solvent interaction analysis (PSA/SIA) assay for prostate cancer (CaP) diagnosis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5053-5053
Author(s):  
S. Vourganti ◽  
M. Stovsky ◽  
L. Ponsky ◽  
M. Siroky ◽  
V. Kipnis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Interaction Analysis ◽  
Sampling Error ◽  
Specific Antigen ◽  
Cleveland Clinic ◽  
Digital Rectal Examination ◽  
Local Therapy ◽  
Total Serum ◽  
Relative Distribution ◽  
Solvent Interaction

5053 Background: We describe the clinical performance of a novel protein structural assay for prostate cancer (CaP) diagnosis. The assay uses Solvent Interaction Analysis (SIA) to accurately detect changes in PSA isoform composition that differentiate benign and malignant disease, independent of total serum PSA (tPSA). Methods: From January 2007 to September 2008, men already undergoing biopsy for accepted clinical criteria at 3 sites [University Hospitals Case Medical Center (Cleveland); Cleveland Clinic (Cleveland); and Veterans Administration Hospital (Boston)] were enrolled in an IRB approved study. Prior to standard transrectal ultrasound (TRUS) guided biopsy, patients received a digital rectal examination with systematic prostate massage followed by collection of voided urine for use in PSA/SIA. The assay determined the relative distribution of the entire heterogeneous PSA isoform population between two coexisting aqueous phases for diagnostic purposes. Results: 222 men were enrolled in the trial. Biopsy results were classified as case (malignant, n = 100) or control (benign, n = 122). Receiver operating characteristic performance results demonstrated AUC of = 0.88 for PSA/SIA and 0.58 for tPSA. At a cut-off value of the composite structural index K = 1.73, PSA/SIA displayed sensitivity = 100%, specificity = 80%, PPV = 83%, and NPV = 100%. For the same patients at tPSA cut-off level of 4 ng/ml, the sensitivity = 82%, specificity = 27%, PPV = 54%, and NPV = 87%. Conclusions: PSA/SIA uniquely exploits the inherent structural heterogeneity in PSA resulting in superior diagnostic performance over conventional biopsy selection criteria. We hypothesize that the high specificity of PSA/SIA is actually underestimated by standard prostate biopsy sampling error. Future trials will assess the utility of the assay in the surveillance of CaP patients after definitive local therapy and other applications in the diagnosis and management of CaP. [Table: see text]

CCP score and risk stratification for prostate cancer patients at biopsy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 47-47 ◽  
Author(s):  
E. David Crawford ◽  
Neal Shore ◽  
Peter T. Scardino ◽  
John W. Davis ◽  
Jonathan D. Tward ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Risk Stratification ◽  
Gleason Score ◽  
Cell Cycle Progression ◽  
Specific Antigen ◽  
Risk Category ◽  
Cycle Progression ◽  
Aggressive Cancer ◽  
Cancer Aggressiveness

47 Background: New prognostic markers for prostate cancer play an important role in addressing the controversies of over diagnosis and treatment. The cell cycle progression score (CCP) (Prolaris, Myriad Genetic Laboratories, Inc.) is a new RNA-based marker, which improved the prediction of prostate cancer aggressiveness in eight separate cohorts. Each one-unit increase in CCP score corresponds with approximately a doubling of the risk of the studied event (recurrence or death from prostate cancer). In this analysis, we characterized the CCP score distribution from our initial CCP signature commercial testing. Methods: Our current laboratory database was evaluated for patients whose biopsy was analyzed with the CCP test and whose clinicopathologic data was collected by the ordering physician. Formalin fixed, prostate biopsy tissue from 1,648 patients diagnosed with adenocarcinoma ordered by more than 300 physicians were analyzed. The CCP score was calculated by measuring the RNA expression of 31 cell cycle progression genes normalized to 15 housekeeping genes. Results: Of the 1,648 samples that contained sufficient carcinoma (more than 0.5mm linear extent), 1,604 (97.3%) provided quality RNA for analysis. This retrospective analysis showed a normal distribution for the CCP score ranging from −2.9 to 3.1. Correlation with Gleason score was r=0.35. A relative classification of cancer aggressiveness based on CCP of approximately1,200 patients from multiple cohorts was developed to interpret how the patient’s CCP score compared to that of patients within the same AUA risk category. The thresholds between each of the five intervals are one unit of CCP score apart, with the "consistent" interval centered at the median CCP score. Based on the CCP score, 27.9% of men had a less aggressive cancer compared to the clinicopathologic prediction and were assigned to a lower risk group while 27.6% of patients had a more aggressive cancer. Conclusions: The CCP signature test is a novel assay that can improve risk stratification for men with prostate adenocarcinoma independent of the Gleason score and prostate-specific antigen level. Over 50% of men initially tested in the commercial assay were assigned to a different risk category than predicted by clinicopathologic features alone.

Evaluation of prostate cancer risk in men with PSA < 1.5.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 64-64
Author(s):  
Whitney N. Stanton ◽  
E. David Crawford ◽  
Paul Arangua ◽  
John Hoenemeyer ◽  
Francisco G. La Rosa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Clinical Information ◽  
Mrna Levels ◽  
Protein Biomarkers ◽  
Cancer Awareness ◽  
Free Psa ◽  
Increased Risk ◽  
Total Psa

64 Background: Prostate Specific Antigen (PSA) screening remains controversial primarily because of over detection and treatment. There is an unmet clinical need to identify patients at increased risk for high-grade (HG – Gleason Score ≥7) prostate cancer (PCa) since PSA has low sensitivity. Combining PSA with well-validated prostate cancer biomarkers (PCM) can improve risk assessment. We investigated the performance of three PCMs (phi – prostate health index, 4KScore, and SelectMDx) on patients with PSA levels < 1.5 ng/mL that represent a “safe zone” where risk of any PCa is rare Methods: 652 men were screened for PCa during the annual Prostate Cancer Awareness Week at the University of Colorado Hospital. This study was supported by Prostate Condition Education Council and the Schramm Foundation. phi is evaluated using p2PSA, total PSA, and free PSA in serum. Phi < 52.7 suggests absence of HG PCa. 4KScore incorporates four kallikrein protein biomarkers: total PSA, free PSA, intact PSA, human kallikrein protein, and clinical information. A 4KScore < 20% suggests absence of HG PCa. The SelectMDx post-DRE urine test measures mRNA levels of the homeobox C6 and distal-less homeobox 1 biomarkers. SelectMDx score of 0% indicates absence of HG PCa. Results: No patients with a PSA < 1.5 had SelectMDx > 0% and/or phi > 52.7. One patient had a 4KScore of 27%, indicating a risk for HG PCa. For patients with PSA between 1.5-3.99, 2.9% (4/135), 7.4% (4/54), and 2.3% (2/85) had positive phi, 4KScore, and SelectMDx results, respectively. Conclusions: Men with PSA <1.5 ng/mL are at very low risk for HG PCa. Men with PSA between 1.5-3.99 with positive PCM results may be referred for further evaluation. [Table: see text]

scholarly journals Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer

2018 ◽  
Vol 46 (2) ◽  
pp. 532-545 ◽  
Author(s):  
Yu-Hui Wang ◽  
Jia Ji ◽  
Bi-Cheng Wang ◽  
Hao Chen ◽  
Zhong-Hua Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Invasion ◽  
Operating Characteristic ◽  
Specific Antigen ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Healthy Individuals ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Non Coding Rnas

Background/Aims: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa). Methods: A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value. Results: Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone. Conclusion: The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.

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