Assessment of Prostate Cancer Aggressiveness: A Metabolomics Evaluation of Urine by NMR Spectroscopy
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Prostate cancer (PCa) is the most common non-skin cancer type among men and one of the leading causes of cancer deaths worldwide [1]. The current diagnostic options of biopsy in combination with PSA-based tests are not conclusive to the aggressiveness of the disease. Novel diagnostic tests for a reliable non-invasive identification of aggressive PCa with high sensitivity and specificity are urgently needed and would be a great advance in clinical routine. At the moment, no single biomarker could be identified to be specific to prostate cancer. In this project, we attempt the identification and validation of urinary metabolite biomarkers and biomarker networks, i.e. high-dimensional classifiers, associated with aggressive prostate cancer.
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![ASSESSMENT OF PROSTATE CANCER AGGRESSIVENESS:
A METABOLOMICS EVALUATION OF URINE BY NMR SPECTROSCOPY
Kdadra Marouane1
, Rudolf Jagdhuber1
, Kremer Werner2
, Eiglsperger Johannes1
& Schiffer Eric1
1
numares AG, Am BioPark 9, 93053 Regensburg, Germany
2
Institute of Biophysics and Physical Biochemistry, University of Regensburg, Regensburg, Germany
BACKGROUND & GOAL
Prostate cancer (PCa) is the most common non-skin cancer type among men and one of the leading
causes of cancer deaths worldwide [1]. The current diagnostic options of biopsy in combination with
PSA-based tests are not conclusive to the aggressiveness of the disease. Novel diagnostic tests for a
reliable non-invasive identification of aggressive PCa with high sensitivity and specificity are urgently
needed and would be a great advance in clinical routine. At the moment, no single biomarker could be
identified to be specific to prostate cancer. In this project, we attempt the identification and validation
of urinary metabolite biomarkers and biomarker networks, i.e. high-dimensional classifiers, associated
with aggressive prostate cancer.
CASE CONTROL DEFINITION
Post surgery Gleason score is used as a response
definition
Indolent Aggressive
1 2 3 4 5 6 7 8 9 10
Training n = 64 n = 238
Test n = 39 n = 183
MATERIALS AND METHODS
urine sample 1H-NMR (600MHz) Raw data
Data processing
• Phasing and baseline correction
• Background treatment
• Normalization by creatinine
Binning
Statistical modeling
• Feature selection
• Cross validation
• Model selection
List of models
RESULTS
Model performance
Test on Evaluation Set
Specificity
Sensitivity
1.0 0.8 0.6 0.4 0.2 0.0
0.00.20.40.60.81.0
AUC
0.660
Literature search
In a recent systematic review article [2], we have summarized a number
of PCa biomarkers which were repeatedly reported and/or independently
validated.
citrate choline 2-aminoadipic acid
glycine spermine glycerol-3-phosphate
proline alanine glycerophosphocholine
histidine uracil phosphocholine
REFERENCES
[1] Gabriel P Haas, Nicolas Delongchamps, Otis W Brawley, Ching Y Wang, and Gustavo de la
Roza. The worldwide epidemiology of prostate cancer: perspectives from autopsy studies.
The Canadian journal of urology, 15(1):3866, 2008.
[2] Marouane Kdadra, Sebastian Höckner, Hing Leung, Werner Kremer, and Eric Schiffer.
Metabolomics biomarkers of prostate cancer: a systematic review. Diagnostics, 9(1):21, 2019.
FUTURE WORK
The next part of the project is to unveil the biology behind this specific step
of the pathological progression by performing a metabolomics, proteomics
and genomics analysis in a systems biology using a holistic and integrative
approach. Clarification of the molecular pathways that may lead to CRPC is
important for discovering novel therapeutic strategies to delay or reverse the
progression of disease.
Figure 1: Prostate cancer plasticity/evolution results in treatment resistance
ACKNOWLEDGEMENT
This project has received funding from the European
Union’s Horizon 2020 research and innovation program
under the Marie Sklodowska-Curie grant agreement No
721746
Contact: marouane.kdadra@numares.com @TransPotITN @numares AG
@TransPot_ITN
Learn more about TransPot](https://image.slidesharecdn.com/conferenceposterporto-191015103437/85/Assessment-of-Prostate-Cancer-Aggressiveness-A-Metabolomics-Evaluation-of-Urine-by-NMR-Spectroscopy-1-320.jpg)
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New Cancer Technology: Is Easy Detection a Reality?
New Cancer Technology: Is Easy Detection a Reality?
Comprehensivereportcannabisextractmovement 131014094154-phpapp01
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Joint FAO/WHO Meeting on Pesticide Residues (JMPR) - Toxicological re-evalua...
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Advances in Diagnosis & Imaging Impacting Cancer Treatment
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Carcinogenicity of Glyphosate A Systematic Review of the Available Evidence
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The potential of liquid biopsies in cancer research
The potential of liquid biopsies in cancer research
Staining of Circulating Tumor Cells - as easy as a blood picture
Staining of Circulating Tumor Cells - as easy as a blood picture
Liquid biopsies- Learn about the newer ways of diagnosing malignancy
Liquid biopsies- Learn about the newer ways of diagnosing malignancy
MCO 2011 - Slide 33 - C. Svedman - Spotlight session - Criteria to evaluate g...
MCO 2011 - Slide 33 - C. Svedman - Spotlight session - Criteria to evaluate g...
Circulating Tumor DNA Detection from Heparinized Plasma Samples by Droplet Di...
Circulating Tumor DNA Detection from Heparinized Plasma Samples by Droplet Di...
A high-throughput approach for multi-omic testing for prostate cancer research
A high-throughput approach for multi-omic testing for prostate cancer research
PMED: APPM Workshop: Data & Analytics in Precision Oncology- Warren Kibbe, Ma...
PMED: APPM Workshop: Data & Analytics in Precision Oncology- Warren Kibbe, Ma...
Similar to Assessment of Prostate Cancer Aggressiveness: A Metabolomics Evaluation of Urine by NMR Spectroscopy
biomarcare_journal.pone.0159522.PDF
This study aimed to develop an unbiased RNA profiling approach for the early detection of colorectal cancer (CRC) and advanced adenomas (AA) using blood samples. The researchers combined a literature review with microarray analysis of circulating RNA purified from plasma to identify RNA biomarker panels. They tested the panels on two cohorts, detecting CRC with 75% sensitivity and 93% specificity using an 8-gene panel, and detecting AA with 60% sensitivity and 87% specificity using a 2-gene panel. The study demonstrates the feasibility of unbiased molecular diagnosis of CRC and AA from blood and introduces circulating RNA profiling as a potential non-invasive screening approach.
PCMT PowerPoint September 2013
The document discusses a prostate cancer test called the Prostate Core Mitomic Test (PCMT) that detects large-scale mitochondrial DNA deletions to help determine if a negative prostate biopsy result represents a true negative or false negative. It provides examples of two patients (Patient A and B) where PCMT identified one as low risk for undiagnosed cancer after a negative biopsy (true negative) while identifying the other as high risk (false negative). The document promotes PCMT as helping physicians confidently stratify patients, avoid unnecessary repeat biopsies, and better manage patient care through early cancer detection.
S13148 019-0757-3
1) Researchers developed a blood-based test called TriMeth for detecting colorectal cancer (CRC) using three tumor-specific DNA methylation markers (C9orf50, KCNQ5, and CLIP4) measured in circulating cell-free DNA.
2) TriMeth was able to detect CRC with 85% sensitivity (218/256 patients) and 99% specificity (176/178 individuals) across two independent plasma cohorts, including 80% sensitivity for stage I CRC.
3) The three markers were identified through a biomarker discovery study involving DNA methylation profiling of over 5000 tumor and blood cell samples, and were validated to be hypermethylated in CRC and adenoma tissues but not in
2013-11-14 NVKCL symposium, Utrecht
The document discusses biomarkers in oncology from cells to systems. It notes that while many biomarkers are discovered, few progress beyond initial publication to clinical validation and diagnostic tests. Reasons for this innovation gap include a lack of integrated biomarker research and development pipelines and challenges in organizing multi-lab validation studies. The talk emphasizes embracing novel omics technologies, considering tumor cells as part of a biological system, and focusing on biomarker validation to address this gap. It provides examples of using mRNA expression profiling and systems-level approaches to stratify and characterize tumors.
tom
This document summarizes preliminary results from an observational study on using [-2]proPSA (p2PSA) to predict early biochemical recurrence after radical prostatectomy.
The study enrolled 64 patients over 15 months to compare p2PSA to total PSA (tPSA) in detecting recurrence. After 12 months, p2PSA detected recurrence in 16 patients (48.5%) compared to only 2 (6.1%) by tPSA. All patients with tPSA recurrence also had elevated p2PSA. p2PSA detected recurrence earlier with a mean of 9 months compared to 12.4 months for tPSA. The findings suggest p2PSA may be more sensitive than
Personalized medicine in prostate cancer care
This document discusses several genomic tests for prostate cancer, including the Oncotype DX prostate cancer test, Prolaris test, and Decipher test. It provides information on what each test is, who it is for, what biological factors it measures, and how the results can help guide treatment decisions, especially for patients with low or intermediate risk prostate cancer considering active surveillance versus immediate treatment. The tests help improve risk stratification by incorporating individual tumor biology beyond standard clinical factors alone.
Targeted Therapy for Uveal Melanoma - Richard Carvajal, MD
Richard Carvajal, MD presents Targeted Therapy for Uveal Melanoma and the Uveal Melanoma Clinical Research Landscape at the 2017 CURE OM Patient & Caregiver Symposium.
blood based bio assays for cancer
Lung cancer is one of the leading causes of cancer deaths. Early detection is challenging due to non-specific symptoms appearing at later stages. Recent studies show blood-based biomarkers like microRNAs and circulating tumor DNA can enable early detection. MicroRNAs miR-486 and miR-150 showed high sensitivity and specificity for detecting NSCLC. Liquid biopsy using amplification and sequencing of cfDNA can detect common oncogene mutations like EGFR from blood, with FDA approval. These minimally invasive blood tests have potential to improve early detection rates and patient outcomes for lung cancer.
Clinical proteomics in diseases lecture, 2014
This document discusses the application of clinical proteomics in disease diagnosis and biomarker discovery. It provides an overview of how proteomics methodologies like mass spectrometry and protein microarrays can be used to identify protein biomarkers for various diseases from body fluids. Specific examples are given of proteomics studies that have discovered protein biomarker patterns or specific proteins that can improve diagnosis of cancers like colorectal cancer and breast cancer compared to single biomarkers. Biomarkers identified for other diseases like Alzheimer's disease and diabetic nephropathy through proteomics are also summarized.
Principles of Cancer Screening
In 1968, Wilson and Jungner (WJ) put together the following criteria of screening approved by the World Health Organization
Principles of Cancer Screening
In 1968, Wilson and Jungner (WJ) put together the following criteria of screening approved by the World Health Organization
Principles of Cancer Screening
In 1968, Wilson and Jungner (WJ) put together the following criteria of screening approved by the World Health Organization
Principles of Cancer Screening
In 1968, Wilson and Jungner (WJ) put together the following criteria of screening approved by the World Health Organization (WHO) [1].
Principles of Cancer Screening
This document discusses principles of cancer screening and summarizes a proposed cancer screening program called CitiScreen. It begins by outlining the Wilson-Jungner criteria for cancer screening approved by the WHO. It then discusses updated screening criteria and reviews the scientific basis for cancer screening through randomized controlled trials and other methods. The document summarizes CitiScreen's goal of comprehensive cancer screening through a combination of technologies and outlines screening patterns for specific cancers like breast, ovarian, lung, and colorectal cancer.
Principles of Cancer Screening
In 1968, Wilson and Jungner (WJ) put together the following criteria of screening approved by the World Health Organization (WHO) [1].
Principles of Cancer Screening
In 1968, Wilson and Jungner (WJ) put together the following criteria of screening approved by the World Health Organization (WHO) [1].
ca cervix screening.pptx
This document presents a study on developing an automated screening technique for cervical cancer using differential interference contrast microscopy and machine learning algorithms. The study aims to differentiate between normal, pre-invasive, and invasive cervical cells based on their morphological features in images. A total of 50 patient samples will be analyzed over 18 months. Statistical analysis will be conducted to calculate sensitivity, specificity, and predictive values of the new screening method. Preliminary results found a sensitivity of 90%, 70%, and 100% for normal, pre-cancer, and cancer cells respectively. The study aims to develop a fast and effective automated cervical cancer screening tool.
Bladder Cancer Diagnostic-Initial Team Project
ACDS Laboratories has developed a new 3-protein biomarker for bladder cancer diagnosis using VEGF, ApoE, and IL-8. The biomarker provides high sensitivity of 90% and specificity of 97% in a study of 127 patients, outperforming current methods. It can be detected through a non-invasive urine test using ELISA, addressing the need for a simple, accurate, and cost-effective diagnostic. Economic analysis shows the biomarker could save over $200 million annually in the US through reducing invasive procedures and long-term monitoring costs compared to current protocols. Based on the strong clinical and economic value, ACDS recommends investing in developing this biomarker.
Advances and Challenges in Refining the Use of Cancer Immunotherapies Through...
Advances and Challenges in Refining the Use of Cancer Immunotherapies Through...PVI, PeerView Institute for Medical Education
Kurt Schalper, MD, PhD, and Edward Garon, MD, MS, prepared useful Practice Aids pertaining to immuno-oncology biomarkers for this CME/MOC activity titled "Advances and Challenges in Refining the Use of Cancer Immunotherapies Through Biomarker Testing: Practical Guidance for Pathologists on the Front Lines of the Immuno-Oncology Revolution." For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2DE3X9J. CME/MOC credit will be available until December 2, 2019.Proteogenomic analysis of human colon cancer reveals new therapeutic opportun...
We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development.
Similar to Assessment of Prostate Cancer Aggressiveness: A Metabolomics Evaluation of Urine by NMR Spectroscopy (20)
Targeted Therapy for Uveal Melanoma - Richard Carvajal, MD
Targeted Therapy for Uveal Melanoma - Richard Carvajal, MD
Advances and Challenges in Refining the Use of Cancer Immunotherapies Through...
Advances and Challenges in Refining the Use of Cancer Immunotherapies Through...
Proteogenomic analysis of human colon cancer reveals new therapeutic opportun...
Proteogenomic analysis of human colon cancer reveals new therapeutic opportun...
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Assessment of Prostate Cancer Aggressiveness: A Metabolomics Evaluation of Urine by NMR Spectroscopy
- 1. ASSESSMENT OF PROSTATE CANCER AGGRESSIVENESS: A METABOLOMICS EVALUATION OF URINE BY NMR SPECTROSCOPY Kdadra Marouane1 , Rudolf Jagdhuber1 , Kremer Werner2 , Eiglsperger Johannes1 & Schiffer Eric1 1 numares AG, Am BioPark 9, 93053 Regensburg, Germany 2 Institute of Biophysics and Physical Biochemistry, University of Regensburg, Regensburg, Germany BACKGROUND & GOAL Prostate cancer (PCa) is the most common non-skin cancer type among men and one of the leading causes of cancer deaths worldwide [1]. The current diagnostic options of biopsy in combination with PSA-based tests are not conclusive to the aggressiveness of the disease. Novel diagnostic tests for a reliable non-invasive identification of aggressive PCa with high sensitivity and specificity are urgently needed and would be a great advance in clinical routine. At the moment, no single biomarker could be identified to be specific to prostate cancer. In this project, we attempt the identification and validation of urinary metabolite biomarkers and biomarker networks, i.e. high-dimensional classifiers, associated with aggressive prostate cancer. CASE CONTROL DEFINITION Post surgery Gleason score is used as a response definition Indolent Aggressive 1 2 3 4 5 6 7 8 9 10 Training n = 64 n = 238 Test n = 39 n = 183 MATERIALS AND METHODS urine sample 1H-NMR (600MHz) Raw data Data processing • Phasing and baseline correction • Background treatment • Normalization by creatinine Binning Statistical modeling • Feature selection • Cross validation • Model selection List of models RESULTS Model performance Test on Evaluation Set Specificity Sensitivity 1.0 0.8 0.6 0.4 0.2 0.0 0.00.20.40.60.81.0 AUC 0.660 Literature search In a recent systematic review article [2], we have summarized a number of PCa biomarkers which were repeatedly reported and/or independently validated. citrate choline 2-aminoadipic acid glycine spermine glycerol-3-phosphate proline alanine glycerophosphocholine histidine uracil phosphocholine REFERENCES [1] Gabriel P Haas, Nicolas Delongchamps, Otis W Brawley, Ching Y Wang, and Gustavo de la Roza. The worldwide epidemiology of prostate cancer: perspectives from autopsy studies. The Canadian journal of urology, 15(1):3866, 2008. [2] Marouane Kdadra, Sebastian Höckner, Hing Leung, Werner Kremer, and Eric Schiffer. Metabolomics biomarkers of prostate cancer: a systematic review. Diagnostics, 9(1):21, 2019. FUTURE WORK The next part of the project is to unveil the biology behind this specific step of the pathological progression by performing a metabolomics, proteomics and genomics analysis in a systems biology using a holistic and integrative approach. Clarification of the molecular pathways that may lead to CRPC is important for discovering novel therapeutic strategies to delay or reverse the progression of disease. Figure 1: Prostate cancer plasticity/evolution results in treatment resistance ACKNOWLEDGEMENT This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 721746 Contact: marouane.kdadra@numares.com @TransPotITN @numares AG @TransPot_ITN Learn more about TransPot