Dimensional reduction based on peak fitting of Raman micro spectroscopy data improves detection of prostate cancer in tissue specimens

Abstract Background Polyomavirus hominis1, also called BK virus (BKV) is a well-known etiological agent of renal transplant nephropathy and cystitis. Recently, it got great attention from the researcher as a principal predisposing factor for different kinds of cancers including prostate cancer (PCa). Thus, this study aims to determine the correlation between BKV infection and PCa through a descriptive case-control based study. Methods A total of 55 paraffin-embedded tissue blocks of patients with PCa and another 55 tissue blocks from BPH patients were obtained. In parallel, respective urine samples were collected from all the cases and controls. The existence of BKV large T antigen (LTAg) was analyzed by Direct Immunofluorescence assay. Only BKV LTAg positive specimens were further analyzed for the presence of viral DNA by using a conventional PCR then subjected to viral load quantitation by using Q-PCR. Result BKV LTAg was identified in 30% (17/55) of cases tissue specimens and only in 7% (4/55) of the controls tissue specimens with P-value 0.002 and Odd ratio 5.7. The conventional PCR detects the BKV DNA in 16 out of 17 cases specimens while only two out of four controls specimens were identified with a viral DNA. The mean of the BKV DNA load was higher significantly among cases 6733 ± 6745 copies/ml when compared to controls 509.0 ± 792.9 copies/m with a p-value of 0.002. Conclusion More BKV prevalence with high viral load was observed in PCa patients tissue compared to BPH specimens. PCa Gleason scores 9 and 7 were the most cancer grades identified with the presence of BKV DNA. Our findings are thus consistent with a significant link between the BKV infection and the PCa risk. Prostate or seminal fluids should be selected as principal specimens for future studies and can, therefore, be designated as screening samples to find early virus evidence in the prostate tissue. Detection of early virus evidence may help to reduce the risk of PCa cancer due to BKV.

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Abstract 2218: Integrated diagnostic methods for detection of multiple gene rearrangements in prostate cancer tissue specimens

10.1158/1538-7445.am2011-2218 ◽

2011 ◽

Author(s):

Connie C. Cortez ◽

Maria Svensson ◽

Raymond Nagle ◽

Karl Garsha ◽

Dea Nagy ◽

...

Keyword(s):

Prostate Cancer ◽

Diagnostic Methods ◽

Cancer Tissue ◽

Gene Rearrangements ◽

Multiple Gene ◽

Prostate Cancer Tissue ◽

Tissue Specimens

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Expression and activity of matrix metalloproteinases-2 and -9 in serum, core needle biopsies and tissue specimens of prostate cancer patients

Virchows Archiv ◽

10.1007/s00428-004-1016-2 ◽

2004 ◽

Vol 444 (6) ◽

Cited By ~ 29

Author(s):

ChristianG. Sauer ◽

Alexandra Kappeler ◽

Monika Sp�th ◽

JensJ. Kaden ◽

MauriceS. Michel ◽

...

Keyword(s):

Prostate Cancer ◽

Matrix Metalloproteinases ◽

Cancer Patients ◽

Core Needle ◽

Tissue Specimens ◽

Expression And Activity

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

Endocrine Related Cancer ◽

10.1530/erc-18-0148 ◽

2018 ◽

Vol 25 (9) ◽

pp. 807-819 ◽

Cited By ~ 6

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.

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RANKL Immunisation Inhibits Prostate Cancer Metastasis by Modulating EMT Through a RANKL-dependent Pathway

10.21203/rs.3.rs-98591/v1 ◽

2020 ◽

Author(s):

Mineon Park ◽

Yong Jin Cho ◽

Bora Kim ◽

Young Jong Ko ◽

Yuria Jang ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Experimental Models ◽

University Hospital ◽

Mitogen Activated Protein Kinase ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Pc3 Cells ◽

Tissue Specimens

Abstract Background: Prostate cancer (PCa) morbidity in the majority of patients is due to metastatic events, which are a clinical obstacle. Therefore, a better understanding of the mechanism underlying metastasis is imperative if we are to develop novel therapeutic strategies. Receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) regulates bone remodelling. RANKL was associated with epithelial-mesenchymal transition (EMT) and expression of metastasis-related genes in PC3 cells. Thus, agents that suppress RANKL signalling may be useful pharmacological treatments. Method: In this study, we proposed a strategy to induce anti-cytokine antibodies using mutant RANKL as an immunogen. Here, we used preclinical experimental models to investigate whether an inactive form of RANKL affects bone metastasis in RANKL-induced PCa.Results: RANKL activation was observed in human PCa tissue specimens. RANKL promoted migration and invasion of PC3 cells through EMT, and induced a significant increase in binding of β-catenin to TCF-4, an EMT-induced transcription factor in PCa cells, via mitogen-activated protein kinase and β-catenin/TCF-4 signalling. Thus, RANKL increased EMT and the metastatic properties of PC3 cells, suggesting a role as a therapeutic target to prevent PCa metastasis. Conclusion: Treatment with mutant RANKL reduced EMT and metastasis of PC3 PCa cells in an experimental metastasis model. Thus, mutant RANKL could serve as a potential vaccine to prevent and treat metastatic PCaTrial registration: Chosun University Hospital, CHOSUN 2020-06-001. Registered 01 June 2020-prospectevely registered, https://hosp.chosun.ac.kr/medi_depart/?site=hospital&mn=151&type=view&catename=IRB

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Molecular Changes in Tissue Proteome during Prostate Cancer Development: Proof-of-Principle Investigation

Diagnostics ◽

10.3390/diagnostics10090655 ◽

2020 ◽

Vol 10 (9) ◽

pp. 655 ◽

Cited By ~ 1

Author(s):

Agnieszka Latosinska ◽

Katarina Davalieva ◽

Manousos Makridakis ◽

William Mullen ◽

Joost P. Schanstra ◽

...

Keyword(s):

Prostate Cancer ◽

In Silico Analysis ◽

Functional Enrichment ◽

Mrna Levels ◽

Proteomics Data ◽

Molecular Alterations ◽

Cancer Transcriptome ◽

Prostate Cancer Development ◽

Fresh Frozen ◽

Tissue Specimens

(1) Background: Prostate cancer (PCa) is characterized by high heterogeneity. The aim of this study was to investigate molecular alterations underlying PCa development based on proteomics data. (2) Methods: Liquid chromatography coupled to tandem mass spectrometry was conducted for 22 fresh-frozen tissue specimens from patients with benign prostatic hyperplasia (BPH, n = 5) and PCa (n = 17). Mann Whitney test was used to define significant differences between the two groups. Association of protein abundance with PCa progression was evaluated using Spearman correlation, followed by verification through investigating the Prostate Cancer Transcriptome Atlas. Functional enrichment and interactome analysis were carried out using Metascape and String. (3) Results: Proteomics analysis identified 1433 proteins, including 145 proteins as differentially abundant between patients with PCa and BPH. In silico analysis revealed alterations in several pathways and hallmarks implicated in metabolism and signalling, represented by 67 proteins. Among the latter, 21 proteins were correlated with PCa progression at both the protein and mRNA levels. Interactome analysis of these 21 proteins predicted interactions between Myc proto-oncogene (MYC) targets, protein processing in the endoplasmic reticulum, and oxidative phosphorylation, with MYC targets having a central role. (4) Conclusions: Tissue proteomics allowed for characterization of proteins and pathways consistently affected during PCa development. Further validation of these findings is required.

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Identification, prioritization, and evaluation of glycoproteins for aggressive prostate cancer using quantitative glycoproteomics and antibody-based assays on tissue specimens

PROTEOMICS ◽

10.1002/pmic.201200541 ◽

2013 ◽

Vol 13 (15) ◽

pp. 2268-2277 ◽

Cited By ~ 30

Author(s):

Jing Chen ◽

Jiefeng Xi ◽

Yuan Tian ◽

George Steven Bova ◽

Hui Zhang

Keyword(s):

Prostate Cancer ◽

Aggressive Prostate Cancer ◽

Tissue Specimens

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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

BioMed Research International ◽

10.1155/2014/972587 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 11

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.

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Blind exploration of the unreferenced transcriptome reveals novel RNAs for prostate cancer diagnosis

10.1101/644104 ◽

2019 ◽

Author(s):

M. Pinskaya ◽

Z. Saci ◽

M. Gallopin ◽

N. H. Nguyen ◽

M. Gabriel ◽

...

Keyword(s):

Prostate Cancer ◽

Rna Sequencing ◽

Single Molecule ◽

The Cancer Genome Atlas ◽

Diagnostic Tools ◽

Bench Test ◽

Specific Expression ◽

High Coverage ◽

Sequencing Technologies ◽

Tissue Specimens

AbstractThe broad use of RNA-sequencing technologies held a promise of improved diagnostic tools based on comprehensive transcript sets. However, mining human transcriptome data for disease biomarkers in clinical specimens is restricted by the limited power of conventional reference-based protocols relying on uniquely mapped reads and transcript annotations. Here, we implemented a blind reference-free computational protocol, DE-kupl, to directly infer RNA variations of any origin, including yet unreferenced RNAs, from high coverage total stranded RNA-sequencing datasets of tissue origin. As a bench test, this protocol was powered for detection of RNA subsequences embedded into unannotated putative long noncoding (lnc)RNAs expressed in prostate cancer tissues. Through filtering and visual inspection of 1,179 candidates, we defined 21 lncRNA probes that were further validated for robust tumor-specific expression by NanoString single molecule-based RNA measurements in 144 tissue specimens. Predictive modeling yielded a restricted probe panel enabling over 90% of true positive detection of cancer in an independent dataset from The Cancer Genome Atlas. Remarkably, this clinical signature made of only 9 unannotated lncRNAs largely outperformed PCA3, the only RNA biomarker approved by the Food and Drug Administration agency, specifically, in detection of high-risk prostate tumors. The proposed reference-free computational workflow is modular, highly sensitive and robust and can be applied to any pathology and any clinical application.

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