scholarly journals Association of Tissue mRNA and Serum Antigen Levels of Members of the Urokinase-Type Plasminogen Activator System with Clinical and Prognostic Parameters in Prostate Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Omar Al-Janabi ◽  
Helge Taubert ◽  
Andrea Lohse-Fischer ◽  
Michael Fröhner ◽  
Sven Wach ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mrna Expression ◽  
Clinicopathological Parameters ◽  
Prognostic Impact ◽  
Serum Samples ◽  
Risk Of Death ◽  
Upa System ◽  
System Components ◽  
Upa Mrna ◽  
Tissue Specimens

The objective was to determine the mRNA expression and protein levels of uPA system components in tissue specimens and serum samples, respectively, from prostate cancer (PCa) patients and to assess their association with clinicopathological parameters and overall survival (OS). The mRNA expression levels of uPA, its receptor (uPAR), and its inhibitor type 1 (PAI-1) were analyzed in corresponding malignant and adjacent nonmalignant tissue specimens from 132 PCa patients by quantitative PCR. Preoperative serum samples from 81 PCa patients were analyzed for antigen levels of uPA system members by ELISA. RNA levels of uPA system components displayed significant correlations with each other in the tumor tissues. A significantly decreased uPA mRNA expression in PCa compared to the corresponding nonmalignant tissue was detected. High uPA mRNA level was significantly associated with a high Gleason score. Elevated concentration of soluble uPAR (suPAR) in serum was significantly associated with a poor OS of PCa patients (P=0.022). PCa patients with high suPAR levels have a significantly higher risk of death (multivariate Cox’s regression analysis;HR=7.12,P=0.027). The association of high suPAR levels with poor survival of PCa patients suggests a prognostic impact of suPAR levels in serum of cancer patients.

Prognostic impact of post-prostatectomy PSA slope determined with a novel, nucleic acid detection immunoassay (NADiA ProsVue) for total PSA.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 47-47 ◽  
Author(s):  
J. W. Moul ◽  
O. J. Semmes ◽  
R. Vessella ◽  
J. E. McDermed ◽  
H. Lilja
Keyword(s):  
Prostate Cancer ◽  
Nucleic Acid Detection ◽  
Prognostic Impact ◽  
Decision Threshold ◽  
New Paradigm ◽  
Serum Samples ◽  
Pilot Studies ◽  
Synthetic Dna ◽  
Total Psa

47 Background: ProsVue is an investigational PSA immunoassay whose reporter antibody is labeled with a synthetic DNA sequence. RT-PCR detects the DNA signal indicating the PSA concentration. Pilot studies showed ProsVue slope (least-squares linear slope of 3 post-RP PSA values) to correctly classify prostate cancer (PC) patients (pts) with no evidence of disease (NED) and clinical progression (CP) using a 2 pg/mL/month (mo) decision threshold. In a retrospective, multicenter clinical trial, we evaluated potential prognostic value of ProsVue slope at this decision threshold. Methods: 392 PC pts having RPs 11/1991 to 8/2001 were studied. Eligibility required first post-RP PSA <100 pg/mL, full pathologic and radiographic data and 3 frozen serum samples drawn 6 weeks to 19.4 mo post-RP. Adjuvant radiotherapy (RT) and/or hormone therapy (HT) was not allowed. CP was documented by positive imaging, biopsy results or PC-related death. Efficacy of ProsVue slope as a prognostic test for NED/CP at a 2 pg/mL/month decision threshold was determined and also examined with regards to Gleason score (GS), pre-RP PSA and final pathology stage. Results: Median (range) of pre-RP PSA was 6.3 (0-60.6) ng/mL and post-RP GS was 7.0 (4-10). 73 pts received neoadjuvant HT. Pathologic stage was pT0-2 (228), pT3 (147), pT4 (17); 116 pts had positive margins and 8 had positive lymph nodes. The 3 PSA values were drawn after a median of 4.9, 8.6 and 12.8 mo and showed median values of 10.7, 23.0 and 50.7 pg/mL, respectively. Calculated sensitivity, specificity, PPV and NPV for a 2 pg/mL/mo ProsVue slope were 75.0%, 96.6%, 81.4% and 95.2%, respectively. Median follow-up (f/u) was 10.5 years. There were 40 deaths (14 from PC). Conclusions: ProsVue provides information previously unknown in post-RP pts. ProsVue slope ≤2pg/mL/mo in the first year is highly associated with NED over long-term f/u. Potential clinical utility may include predicting pts not requiring long-term oncologic f/u and predicting a need for post-RP adjuvant RT. ProsVue slope may become a new paradigm for identifying those patients at reduced risk for recurrence of prostate cancer post-RP. Further studies are planned to address these questions. [Table: see text]

scholarly journals Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer

2018 ◽  
Vol 25 (9) ◽  
pp. 807-819 ◽  
Author(s):  
Matias Knuuttila ◽  
Arfa Mehmood ◽  
Jenni Mäki-Jouppila ◽  
Henrik Ryberg ◽  
Pekka Taimen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Alternative Pathway ◽  
Prostate Tissue ◽  
Cancer Therapies ◽  
Serum Samples ◽  
Androgen Metabolism ◽  
Tissue Specimens ◽  
Regulated Gene Expression ◽  
Benign Prostate

Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral dihydrotestosterone (DHT) concentrations were significantly higher in the cancerous tissues compared to benign prostate (P < 0.001). The tissue/serum ratios of androgens were highly variable between the patients, indicating individual patterns of androgen metabolism and/or uptake of androgens within the prostate tissue. An unsupervised hierarchical clustering analysis of intratissue androgen concentrations indicated that transmembrane protease, serine 2/ETS-related gene (TMPRSS2-ERG)-positive patients have different androgen profiles compared to TMPRSS2-ERG-negative patients. TMPRSS2-ERG gene fusion status was also associated with an enhanced androgen-regulated gene expression, along with altered intratumoral androgen metabolism, demonstrated by reduced testosterone concentrations and increased DHT/testosterone ratios in TMPRSS2-ERG-positive tumors. TMPRSS2-ERG-positive and -negative prostate cancer specimens have distinct intratumoral androgen profiles, possibly due to activation of testosterone-independent DHT biosynthesis via the alternative pathway in TMPRSS2-ERG-positive tumors. Thus, patients with TMPRSS2-ERG-positive prostate cancer may benefit from novel inhibitors targeting the alternative DHT biosynthesis.

scholarly journals Human Papillomavirus (HPV) Infection As an Emerging Risk Factor in Prostate Cancer

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 24s-24s
Author(s):  
N. Singh ◽  
A. Josefsson ◽  
S. Hussain ◽  
J. Hugosson
Keyword(s):  
Prostate Cancer ◽  
Sexually Transmitted Infection ◽  
Hpv Infection ◽  
Clinical Staging ◽  
Clinicopathological Parameters ◽  
Prognostic Impact ◽  
Preoperative Radiation ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
Prostate Carcinogenesis

Background: Epidemiologic investigations confirm that prostate tissue is prone to sexually transmitted infection and human papilloma virus (HPV) is the most common sexually transmitted infection. Owing to the controversy on the role of HPV infection in prostate carcinogenesis, it is appropriate to determine and validate the prevalence of HPV infection in a controlled prospective study, and its role in prostate carcinogenesis. It is crucial to investigate the prognostic impact of HPV infection in prostate cancer from a clinical point of view. Aim: The overall aim of our research is to address the possibility of using therapeutic interventions against HPV infection in young boys to prevent the development of prostate cancer in their older age. Establishment of clinical importance of HPV infection in prostate cancer and its prognostic impact for overall survival. Methods: The prostate cancer tissue specimens were obtained from Sahlgrenska University Hospital, Sahlgrenska Academy (SA), Gothenburg, Sweden. The exclusion criteria included patients undergoing any preoperative radiation or chemotherapy. Only histopathologically confirmed cases were processed for DNA, protein and RNA extraction. Histopathological grades and clinical staging was evaluated by pathologists using the Gleason scoring system for prostate cancer. The study is approved by the ethics committee of the institute. High molecular-weight genomic DNA was isolated from tumor/control tissue samples and were subjected to PCR genotyping for detection of the viral DNA. Cases and controls was compared using univariate methods. An independent t-test was performed for the comparison of clinicopathological parameters. Results: The pilot study identified HPV infection in advanced grade of prostate cancer cases in Sweden. HPV infection was identified in 57% of the prostate cancer cases with advanced pathologic grade in Swedish men compared with 11% in the normal controls. The investigation comprised of detailed analysis of the correlation between the clinical parameters and HPV genotyping. Conclusion: The research investigation substantiates the clinical significance of HPV infection in prostate carcinogenesis that has been underestimated till date. The research investigation was funded by Swedish Research Council (Vetenskaprådet) Grant no. 2015-06705.

Prognostic impact of clinical and pathologic criteria in neuroendocrine and aggressive variant prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 268-268
Author(s):  
Beerinder S. Karir ◽  
Panagiotis J. Vlachostergios ◽  
Paul J. Christos ◽  
Victor RA Febles ◽  
Kavya Pinto-Chengot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Value ◽  
Rank Test ◽  
Prognostic Impact ◽  
Test Results ◽  
Single Institution ◽  
Risk Of Death ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Aggressive Variant

268 Background: Various clinical and pathologic criteria have been proposed to identify neuroendocrine (NE) or aggressive variant (AV) prostate cancer (PC). We assessed the prognostic value of clinical parameters in a single-institution cohort. Methods: An IRB-approved database was screened for clinical and/or pathologic criteria (Table 1) for NE/AV PC. Patients with advanced CRPC not meeting any of the criteria served as contemporary controls. Overall survival (OS) for each group was assessed using Kaplan-Meier method and comparisons with log-rank test. Results: 249 men were identified, median age 71.5 (45.1-90.8 years). 145 patients met at least 1 criterion suggestive of NE/AV PC, whereas 104 were CRPC only. Median OS for each subgroup, the combined NE/AV PC group, and the CRPC cohort are provided in Table 1. OS for NE/AV PC vs. CRPC cohort was 25.4 vs 33 months (p = 0.26). Patients with parenchymal brain metastasis had the worst survival of 5.2 mo [95%CI 2.1, 8.3]. On multivariate analysis, bulky high-grade disease in prostate/pelvis carried the highest risk of death (HR 1.71 [1.07, 2.74; p = 0.02]). Conclusions: A number of clinical and pathologic criteria have been used to define NE/AV PC for clinical practice or trial enrollment. Some criteria are associated with a shorter survival than others. Additional studies are warranted to further define both prognostic and molecularly defined subgroups. [Table: see text]

scholarly journals Quantitative Analysis of Human Kallikrein 5 (KLK5) Expression in Prostate Needle Biopsies: An Independent Cancer Biomarker

2009 ◽  
Vol 55 (5) ◽  
pp. 904-913 ◽  
Author(s):  
Dimitrios Korbakis ◽  
Alkiviades K Gregorakis ◽  
Andreas Scorilas
Keyword(s):  
Prostate Cancer ◽  
Mrna Expression ◽  
Early Stage ◽  
Mrna Level ◽  
Housekeeping Gene ◽  
Significant Negative Correlation ◽  
Diagnosis And Prognosis ◽  
Pcr Method ◽  
Total Psa ◽  
Tissue Specimens

Abstract Background: Kallikrein 5 (KLK5), a recently cloned member of the kallikrein family, codes for the secreted protein KLK5. Active KLK5 protein has a trypsin activity, and the expression of KLK5 gene seems to be regulated by steroid hormones. We performed an expression analysis and clinical evaluation of the KLK5 gene, at the mRNA level, in prostate needle biopsies. Methods: We examined KLK5 mRNA concentrations in 103 prostate tissue specimens. After testing of RNA quality, cDNA was prepared by reverse transcription. A highly sensitive quantitative real-time PCR (qRT-PCR) method for KLK5 mRNA quantification was developed using the SYBR Green chemistry. GAPDH was used as a housekeeping gene. Results: Specimens from patients with benign prostatic hyperplasia (BPH) showed higher levels of KLK5 mRNA expression than those from patients with prostate cancer (PCa) (P = 0.024). ROC analysis demonstrated that KLK5 expression had significant discriminatory value between BPH and PCa (AUC 0.64; P = 0.016). KLK5 mRNA expression showed a statistically significant negative correlation with the total PSA serum concentration in the PCa patients (P = 0.003). Early-stage tumors showed higher KLK5 expression than late-stage ones (P = 0.014), whereas KLK5 expression was negatively correlated to Gleason score (P = 0.005). Conclusions: KLK5 mRNA, analyzed by quantitative PCR in prostate needle biopsies, could be an independent biomarker for the differential diagnosis and prognosis in prostate cancer.

scholarly journals DNA tetrahedron-mediated immune-sandwich assay for rapid and sensitive detection of PSA through a microfluidic electrochemical detection system

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dezhi Feng ◽  
Jing Su ◽  
Yi Xu ◽  
Guifang He ◽  
Chenguang Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Reaction Time ◽  
Electrochemical Detection ◽  
Detection System ◽  
Detection Performance ◽  
Pdms Layer ◽  
Microfluidic Chips ◽  
Serum Samples ◽  
Gold Nanoflowers ◽  
Dna Tetrahedron

AbstractProstate-specific antigen (PSA) is the most widely used biomarker for the early diagnosis of prostate cancer. Existing methods for PSA detection are burdened with some limitations and require improvement. Herein, we developed a novel microfluidic–electrochemical (μFEC) detection system for PSA detection. First, we constructed an electrochemical biosensor based on screen-printed electrodes (SPEs) with modification of gold nanoflowers (Au NFs) and DNA tetrahedron structural probes (TSPs), which showed great detection performance. Second, we fabricated microfluidic chips by DNA TSP-Au NF-modified SPEs and a PDMS layer with designed dense meandering microchannels. Finally, the μFEC detection system was achieved based on microfluidic chips integrated with the liquid automatic conveying unit and electrochemical detection platform. The μFEC system we developed acquired great detection performance for PSA detection in PBS solution. For PSA assays in spiked serum samples of the μFEC system, we obtained a linear dynamic range of 1–100 ng/mL with a limit of detection of 0.2 ng/mL and a total reaction time <25 min. Real serum samples of prostate cancer patients presented a strong correlation between the “gold-standard” chemiluminescence assays and the μFEC system. In terms of operation procedure, cost, and reaction time, our method was superior to the current methods for PSA detection and shows great potential for practical clinical application in the future.

Independent prognostic impact of plasma NCOA2 alterations in metastatic castration‐resistant prostate cancer

The Prostate ◽  
2021 ◽  
Author(s):  
Heidi Fettke ◽  
Edmond M. Kwan ◽  
Patricia Bukczynska ◽  
Jason A. Steen ◽  
Maria Docanto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Impact ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant
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