An Innovative Prostate Cancer Detection Method via Model Checking

Abstract Purpose: one of typical cancer among men is the prostate tumour. This is the reason why the screening and the early detection is a crucial task to obtain a diagnosis and a subsequent therapy in the shortest possible time. Materials and Methods: in this paper, with the aim to help radiologists and pathologists for a prompt diagnosis, a method for detecting prostate cancer is proposed. Our analysis starts from the magnetic resonances images (coronal and axial planes), building a labelled transition system for coronal slices and another one for axial, which takes into account a number of non invasive radiomic features. Thus, a set of formulae in temporal logic characterizing the prostate cancer is verified through the model checking technique, to detect the prostate cancer. The proposed method considers magnetic resonance images without the Region Of Interest. This represents one of the major novelty of the method. Results: the proposed method is evaluated on a data-set composed of 40 patients, obtaining very interesting performances in the discrimination between affected and not affected prostate cancer patients. Conclusion: the study confirms the effectiveness of the formal methods to discriminate between cancerous and benign prostate MRIs with a method not requiring the ROI of the cancerous area, by obtaining a sensitivity and a specificity equal to 1.

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Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up

BMC Medicine ◽

10.1186/s12916-020-01834-0 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Heather Johnson ◽

Jinan Guo ◽

Xuhui Zhang ◽

Heqiu Zhang ◽

Athanasios Simoulis ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Cancer Diagnosis ◽

Multivariate Logistic Regression Analysis ◽

Gene Panel ◽

Urine Test ◽

Non Invasive ◽

Clinically Significant ◽

Benign Prostate

Abstract Background Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. Methods Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRT-PCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. Results The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963–0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929–0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956–0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980–0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947–0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. Conclusions The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.

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Novel non-invasive biomarkers that distinguish between benign prostate hyperplasia and prostate cancer

BMC Cancer ◽

10.1186/s12885-015-1284-z ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 22

Author(s):

Andrej Jedinak ◽

Adam Curatolo ◽

David Zurakowski ◽

Simon Dillon ◽

Manoj K Bhasin ◽

...

Keyword(s):

Prostate Cancer ◽

Benign Prostate Hyperplasia ◽

Prostate Hyperplasia ◽

Non Invasive ◽

Benign Prostate

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Characterisation of the main PSA glycoforms in aggressive prostate cancer

Scientific Reports ◽

10.1038/s41598-020-75526-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Anna Gratacós-Mulleras ◽

Adrià Duran ◽

Akram Asadi Shehni ◽

Montserrat Ferrer-Batallé ◽

Manel Ramírez ◽

...

Keyword(s):

Prostate Cancer ◽

Blood Serum ◽

Specific Antigen ◽

Serum Levels ◽

Neoplastic Progression ◽

Healthy Individuals ◽

Hydrophilic Interaction ◽

Glycosylation Pattern ◽

Non Invasive ◽

Benign Prostate

Abstract Serum levels of prostate specific antigen (PSA) are commonly used for prostate cancer (PCa) detection. However, their lack of specificity to distinguish benign prostate pathologies from PCa, or indolent from aggressive PCa have prompted the study of new non-invasive PCa biomarkers. Aberrant glycosylation is involved in neoplastic progression and specific changes in PSA glycosylation pattern, as the reduction in the percentage of α2,6-sialic acid (SA) are associated with PCa aggressiveness. In this study, we have characterised the main sialylated PSA glycoforms from blood serum of aggressive PCa patients and have compared with those of standard PSA from healthy individuals’ seminal plasma. PSA was immunoprecipitated and α2,6-SA were separated from α2,3-SA glycoforms using SNA affinity chromatography. PSA N-glycans were released, labelled and analysed by hydrophilic interaction liquid chromatography combined with exoglycosidase digestions. The results showed that blood serum PSA sialylated glycoforms containing GalNAc residues were largely increased in aggressive PCa patients, whereas the disialylated core fucosylated biantennary structures with α2,6-SA, which are the major PSA glycoforms in standard PSA from healthy individuals, were markedly reduced in aggressive PCa. The identification of these main PSA glycoforms altered in aggressive PCa opens the way to design specific strategies to target them, which will be useful to improve PCa risk stratification.

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Abstract 3188: Discovery and validation of non-invasive biomarkers for benign prostate hyperplasia and prostate cancer

10.1158/1538-7445.am2011-3188 ◽

2011 ◽

Author(s):

Adam S. Curatolo ◽

Roopali Roy ◽

Andrej Jedinak ◽

Kevin Loughlin ◽

Michael Meyers ◽

...

Keyword(s):

Prostate Cancer ◽

Benign Prostate Hyperplasia ◽

Prostate Hyperplasia ◽

Non Invasive ◽

Benign Prostate

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Intragenic expression profile in tissue and plasma for the detection of TMPRSS2 rearrangements associated with prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5162 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5162-5162

Author(s):

H. R. Sanders ◽

H. Li ◽

K. Z. Qu ◽

Z. J. Zhang ◽

A. D. Sferruzza ◽

...

Keyword(s):

Prostate Cancer ◽

High Specificity ◽

Ffpe Tissue ◽

Rt Pcr ◽

Multiple Partner ◽

Prostate Hyperplasia ◽

Non Invasive ◽

Normal Individuals ◽

Plasma Rna ◽

Benign Prostate

5162 Background: TMPRSS2 gene rearrangements have been reported in 40%-85% of prostate cancer (PCa) patients and have not been found in normal individuals or those with benign prostate hyperplasia (BPH). However, multiple partner genes, including ETS transcription genes, and breakpoints have been reported. We developed an assay based on TMPRSS2 5′ and 3′ intragenic differential expression (IDE) to potentially serve as a diagnostic or prognostic marker for PCa. Methods: We analyzed TMPRSS2 in FFPE tissue from 20 patients (9 PCa and 11 BPH) and plasma from 42 patients (32 PCa and 10 BPH). IDE was expressed as a ratio of 3′:5′ transcript levels which were determined by real-time RT-PCR using distinct primer/probe sets. A normal 3′:5′ ratio (≥30) was established by comparing nonmalignant cells to tumor cells from FFPE tissue. This cutoff was subsequently used to identify abnormal ratios in plasma specimens. Results: In FFPE tissue, 100% of PCa samples had a 3′:5′ratio <30 and 91% of BPH samples were ≥30 ( Table ). RNA in 48% of plasma samples passed our QC criteria for acceptability. The 3′:5′ ratios were <30 in 47% and ≥30 in 6.7% PCa plasma. Conclusions: By measuring IDE, we are not limited to screening for known TMPRSS2/ETS gene translocations. In tissue, this approach enabled us to identify patients with PCa vs. BPH with high specificity. Although work is needed to improve plasma RNA quality, IDE of plasma TMPRSS2 may be a useful non-invasive diagnostic or prognostic tool. [Table: see text] No significant financial relationships to disclose.

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Integrin Alpha V in Urine: A Novel Noninvasive Marker for Prostate Cancer Detection

Frontiers in Oncology ◽

10.3389/fonc.2020.610647 ◽

2021 ◽

Vol 10 ◽

Author(s):

Marina Y. Zemskova ◽

Maria V. Marinets ◽

Andrey V. Sivkov ◽

Julia V. Pavlova ◽

Andrey N. Shibaev ◽

...

Keyword(s):

Prostate Cancer ◽

Urine Analysis ◽

Specific Antigen ◽

High Specificity ◽

Control Group ◽

Prostate Hyperplasia ◽

Non Invasive ◽

Diagnostic Potential ◽

Noninvasive Biomarker ◽

Benign Prostate

Prostate cancer (PCa) diagnosis based on patient urine analysis provides non-invasive and promising method as compared to biopsy and a prostate-specific antigen (PSA) test. This study was conceived to investigate whether Integrin alpha V (ITGAV) protein is present in urine and assess the urinary ITGAV diagnostic potential for PCa. Materials and Methods: Urinary ITGAV expression was determined by Western blot analysis and quantified by ELISA in urine from men with PCa (n = 47), benign prostate hyperplasia (n = 42) and age-matched controls (n = 22). Results: The level of ITGAV protein was significantly lower in PCa urine samples as compared to those in the control group (p < 0.00001). The decrease of ITGAV in urine was highly predictive of PCa with 91.5% sensitivity, 91.4% specificity, 0.93 area under the ROC curve, and its specificity was better than that of serum PSA. Conclusion: Urinary ITGAV provides a novel noninvasive biomarker with high specificity.

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Expression of Urokinase and Its Receptor in Invasive and Non-Invasive Prostate Cancer Cell Lines

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646340 ◽

1992 ◽

Vol 68 (06) ◽

pp. 662-666 ◽

Cited By ~ 38

Author(s):

W Hollas ◽

N Hoosein ◽

L W K Chung ◽

A Mazar ◽

J Henkin ◽

...

Keyword(s):

Prostate Cancer ◽

Steady State ◽

Cell Surface ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Lncap Cells ◽

Prostate Cancer Cell Lines ◽

Non Invasive

SummaryWe previously reported that extracellular matrix invasion by the prostate cancer cell lines, PC-3 and DU-145 was contingent on endogenous urokinase being bound to a specific cell surface receptor. The present study was undertaken to characterize the expression of both urokinase and its receptor in the non-invasive LNCaP and the invasive PC-3 and DU-145 prostate cells. Northern blotting indicated that the invasive PC-3 cells, which secreted 10 times more urokinase (680 ng/ml per 106 cells per 48 h) than DU-145 cells (63 ng/ml per 106 cells per 48 h), had the most abundant transcript for the plasminogen activator. This, at least, partly reflected a 3 fold amplification of the urokinase gene in the PC-3 cells. In contrast, urokinase-specific transcript could not be detected in the non-invasive LNCaP cells previously characterized as being negative for urokinase protein. Southern blotting indicated that this was not a consequence of deletion of the urokinase gene. Crosslinking of radiolabelled aminoterminal fragment of urokinase to the cell surface indicated the presence of a 51 kDa receptor in extracts of the invasive PC-3 and DU-145 cells but not in extracts of the non-invasive LNCaP cells. The amount of binding protein correlated well with binding capacities calculated by Scatchard analysis. In contrast, the steady state level of urokinase receptor transcript was a poor predictor of receptor display. PC-3 cells, which were equipped with 25,000 receptors per cell had 2.5 fold more steady state transcript than DU-145 cells which displayed 93,000 binding sites per cell.

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