Establishment of Biomarker Panel May Lead to Rapid Tests for Early Diagnosis of Pancreatic Cancer
|
By LabMedica International staff writers Posted on 10 Apr 2016 |
|
Image: Micrograph of pancreatic ductal adenocarcinoma (the most common type of pancreatic cancer) (Photo courtesy of Wikimedia Commons).
A panel comprising five genetic biomarkers was shown to accurately differentiate among tissues from pancreatic tumors and those taken from various non-malignant sources.
Investigators at Beth Israel Deaconess Medical Center (Boston, MA, USA) applied innovative data normalization and gene selection approaches to analyze a number of publicly available pancreatic cancer gene expression datasets. They combined the statistical power of multiple genomic studies while masking their variability and batch effects to identify robust early diagnostic biomarkers of pancreatic cancer.
The investigators established a panel comprising the genes TMPRSS4 (Transmembrane protease, serine 4), AHNAK2 (AHNAK nucleoprotein 2), POSTN (Periostin), ECT2 (Epithelial cell transforming 2), and SERPINB5 (Serpin peptidase inhibitor, clade B (ovalbumin), member 5) that achieved on average 95% sensitivity and 89% specificity in discriminating pancreatic ductal adenocarcinoma (PDAC) from non-tumor samples in four training sets and similar performance in five independent validation datasets. The five-gene classifier accurately discriminated PDAC from chronic pancreatitis, other cancers, and non-tumor samples from PDAC precursors in three independent datasets.
PDAC-specific expression of the biomarker panel was measured by qRT-PCR (qualitative real-time PCR) in microdissected patient-derived FFPE (formalin-fixed, paraffin-embedded) tissues. Cell-based assays were then used to assess the impact of two of the biomarkers, TMPRSS4 and ECT2, on PDAC cells.
Results revealed that knock-down of TMPRSS4 and ECT2 reduced PDAC soft agar growth and cell viability, and TMPRSS4 knockdown also blocked PDAC migration and invasion.
“Pancreatic cancer is a devastating disease with a death rate close to the incidence rate,” said senior author Dr. Towia Libermann, professor of medicine at Beth Israel Deaconess Medical Center. “Because more than 90% of pancreatic cancer cases are diagnosed at the metastatic stage, when there are only limited therapeutic options, earlier diagnosis is anticipated to have a major impact on extending life expectancy for patients. There has been a lack of reliable markers, early indicators, and risk factors associated with pancreatic cancer, but this new way of differentiating between healthy and malignant tissue offers hope for earlier diagnosis and treatment.”
“Because these five genes are turned on so early in the development of pancreatic cancer, they may play roles as drivers of this disease and may be exciting targets for therapies,” said Dr. Libermann. “Moving forward, we will explore the potential to convert this tissue-based diagnostic into a noninvasive blood or urine test.”
The study was published in the March 16, 2016, online edition of the journal Oncotarget.
Related Links:
Beth Israel Deaconess Medical Center
Investigators at Beth Israel Deaconess Medical Center (Boston, MA, USA) applied innovative data normalization and gene selection approaches to analyze a number of publicly available pancreatic cancer gene expression datasets. They combined the statistical power of multiple genomic studies while masking their variability and batch effects to identify robust early diagnostic biomarkers of pancreatic cancer.
The investigators established a panel comprising the genes TMPRSS4 (Transmembrane protease, serine 4), AHNAK2 (AHNAK nucleoprotein 2), POSTN (Periostin), ECT2 (Epithelial cell transforming 2), and SERPINB5 (Serpin peptidase inhibitor, clade B (ovalbumin), member 5) that achieved on average 95% sensitivity and 89% specificity in discriminating pancreatic ductal adenocarcinoma (PDAC) from non-tumor samples in four training sets and similar performance in five independent validation datasets. The five-gene classifier accurately discriminated PDAC from chronic pancreatitis, other cancers, and non-tumor samples from PDAC precursors in three independent datasets.
PDAC-specific expression of the biomarker panel was measured by qRT-PCR (qualitative real-time PCR) in microdissected patient-derived FFPE (formalin-fixed, paraffin-embedded) tissues. Cell-based assays were then used to assess the impact of two of the biomarkers, TMPRSS4 and ECT2, on PDAC cells.
Results revealed that knock-down of TMPRSS4 and ECT2 reduced PDAC soft agar growth and cell viability, and TMPRSS4 knockdown also blocked PDAC migration and invasion.
“Pancreatic cancer is a devastating disease with a death rate close to the incidence rate,” said senior author Dr. Towia Libermann, professor of medicine at Beth Israel Deaconess Medical Center. “Because more than 90% of pancreatic cancer cases are diagnosed at the metastatic stage, when there are only limited therapeutic options, earlier diagnosis is anticipated to have a major impact on extending life expectancy for patients. There has been a lack of reliable markers, early indicators, and risk factors associated with pancreatic cancer, but this new way of differentiating between healthy and malignant tissue offers hope for earlier diagnosis and treatment.”
“Because these five genes are turned on so early in the development of pancreatic cancer, they may play roles as drivers of this disease and may be exciting targets for therapies,” said Dr. Libermann. “Moving forward, we will explore the potential to convert this tissue-based diagnostic into a noninvasive blood or urine test.”
The study was published in the March 16, 2016, online edition of the journal Oncotarget.
Related Links:
Beth Israel Deaconess Medical Center
Platinum Member
Automated Coagulation Analyzer
Hemolumi H6
Gold Member
Quantitative POC Immunoassay Analyzer
EASY READER+
CMV CLIA Diagnostic
CLIA CMV IgA Screen Group
Urine Analyzer
respons® UDS100
Latest Pathology News
- Simple Test Could Reduce the Need for Invasive Uterine Cancer Checks
- Tumor Blood Vessel Features May Help Predict Colorectal Cancer Survival
- Multimodal AI Improves Breast Cancer Recurrence Risk Prediction Beyond Standard Genomic Testing
- Machine Learning Cytology Tool Improves Cancer Cell Identification
- CAP Updates Cancer Protocols to Refine Breast Cancer Biomarker Reporting and GIST Molecular Testing
- Tumor Budding Grading May Predict Chemotherapy Benefit in Resected Lung Squamous Cancer
- AI Spatial Analysis of Routine Slides Helps Predict Pancreatic Cancer Recurrence
- Hybrid Computational Imaging Method Improves Digital Pathology Resolution
- FDA Clearance Expands Digital Pathology Options for Clinical Laboratories
- Label-Free Imaging Reveals Hidden Immune Activity in Blood Samples
- AI Tool Improves Prediction of Immunotherapy Response in Lung Cancer
- New Journal Addresses Evolving Needs in Clinical and Translational Pathology
- AI Matches Pathologists in Predicting Breast Cancer Prognosis from Immune Cells
- AI-Pathologist Framework Improves Accuracy and Reliability in Cancer Diagnosis
- New Review Highlights Intelligent Agents as Next Step for Digital Pathology
- Simple Immunohistochemical Size Ratio Improves Classification of Primary Aldosteronism
Channels
Clinical Chemistry
view channel
Prehospital Blood Test Could Reduce Emergency Transfers for Chest Pain
Chest pain leads to ambulance transport to an emergency department for about 95% of patients, although only a minority have a serious cardiac condition. Troponin testing helps assess heart muscle damage,... Read more
First-of-Its-Kind Rapid Blood Test Gains CE Mark to Support Prehospital Stroke Triage
Rapid stroke identification before hospital arrival is critical because treatment efficacy declines with every minute of delay. However, definitive assessment typically requires hospital-based imaging,... Read more
Multi-Cancer Blood Test Expands Detection to Cancers Lacking Routine Screening Options
Many lethal cancers lack routine screening and are often diagnosed only after symptoms emerge, limiting curative options. Standard programs in the United States cover a small subset of malignancies, leaving... Read more
Blood Test Could Guide Drug Selection to Prevent Repeat Heart Attacks and Strokes
Secondary prevention after myocardial infarction or stroke relies on antiplatelet therapy, yet responses vary widely and both recurrent thrombosis and bleeding remain persistent risks. In the United Kingdom,... Read moreMolecular Diagnostics
view channel
Blood Test Stratifies Prostate and Breast Cancer Risk Years Before Diagnosis
Cancer is the second leading cause of death globally, and late diagnosis contributes substantially to mortality. Routine screening is available for only a few cancer types, while other early detection... Read more
CSF Liquid Biopsy Could Help Distinguish Cancer from Autoimmune Brain Inflammation
Autoimmune encephalitis can cause memory and behavioral changes, seizures, and altered consciousness, but diagnosis can be challenging because cancers involving the brain and central nervous system may... Read more
Mpox Analysis Reveals Substantial Suspected False Positives Associated with Contamination
Reliable confirmation of mpox can be difficult where multiple rash-causing illnesses co-circulate and laboratory capacity is limited. Although PCR is central to case detection, contamination during specimen... Read more
Liquid Biopsy Shows Promise for Detecting and Monitoring Malignant Nerve Sheath Tumors
Malignant peripheral nerve sheath tumor (MPNST) is one of the most serious cancers affecting people with neurofibromatosis type 1 (NF1), yet timely recognition remains difficult. Clinicians often struggle... Read moreHematology
view channel
New Donor Genetic Marker May Help Predict Stem Cell Transplant Success
Donor selection for hematopoietic stem cell transplantation plays a major role in relapse risk and survival for patients with blood cancers and other blood disorders. Despite advances in genotyping, uncertainty... Read more
Updated Ferritin Thresholds Improve Detection of Iron Deficiency
Iron deficiency is one of the most common health conditions worldwide, yet its nonspecific symptoms can delay diagnosis for months. Variation in testing practices and ferritin thresholds may contribute... Read more
Immunology
view channel
Werfen Expands Automated APS Testing with FDA-Cleared and CE-Marked IgA Reagent
Antiphospholipid syndrome (APS) is an autoimmune disorder associated with thrombosis and pregnancy complications, but its symptoms can overlap with those of other conditions, complicating diagnosis.... Read more
Blood Biomarker May Predict Colitis Risk in Checkpoint Inhibitor Therapy
Immune checkpoint inhibitors can trigger immune-related colitis that leads to severe diarrhea, abdominal pain, and treatment interruptions. Clinicians currently lack validated tools to identify which patients... Read more
Blood EBV Activity Biomarkers May Predict Multiple Sclerosis Relapse Months Ahead
Predicting relapse in multiple sclerosis (MS) remains difficult, limiting opportunities for timely intervention and monitoring. Although many people harbor latent Epstein-Barr virus (EBV), growing evidence... Read more
Microbiology
view channel
New Urine Test Expands Mycotoxin Analysis to 31 Markers for Broader Exposure Assessment
Clinical evaluation of mold exposure increasingly relies on urinary mycotoxin testing, but limited marker coverage and metabolite masking can make results more difficult to interpret. Broader analysis... Read more
Collaboration Targets Blood-Based Ebola Detection Outside Central Laboratories
Co-Diagnostics, Inc. (Salt Lake City, UT, USA) and ReadyGo Diagnostics Ltd. (Bath, UK) have initiated a collaboration to evaluate ReadyGo’s GoCollect with the Co-Dx PCR platform for blood-based molecular... Read more
Technology
view channel
ADLM Calls for CLIA Updates to Support Safe AI Use in Laboratory Medicine
Clinical laboratories increasingly use artificial intelligence to verify, interpret, and report results, but safeguards under the Clinical Laboratory Improvement Amendments (CLIA) were designed in 1992.... Read more
Multimodal AI Framework Aims to Guide Cancer Immunotherapy Decisions
Cancer immunotherapy has reshaped oncology, but heterogeneous responses and immune-related toxicities continue to complicate routine decision-making. Standard biomarkers, including programmed death-ligand... Read more
New Multipurpose Centrifuge Combines High Capacity with Sustainable Cooling
Laboratories often need centrifugation that accommodates multiple vessel formats while maintaining controlled temperatures to protect sensitive samples. Intuitive controls and repeatable operation can... Read more
Bacterial Vesicle Expression System Streamlines Production of Cancer Diagnostic Proteins
Recombinant proteins are central to many cancer diagnostics and therapies, but numerous targets remain difficult and costly to produce because they are unstable, toxic to microbial hosts, or require precise folding.... Read moreIndustry
view channel
New UK Collaboration Expands Access to Integrated Alzheimer’s Diagnostic Testing
C2N Diagnostics and Cambridge Cognition have partnered with The Alzheimer’s Trust to create an integrated pathway aimed at supporting earlier and more accurate diagnosis of Alzheimer’s disease and related dementias.... Read more
Multi-Cancer Early Detection Test Wins FDA Panel Backing for Approval
GRAIL’s Galleri multi-cancer early detection (MCED) test was reviewed by the Molecular and Clinical Genetics Devices Panel of the U.S. Food and Drug Administration’s (FDA) Medical Devices Advisory Committee.... Read more
Siemens Healthineers and Novo Collaborate to Expand Access to Noninvasive Liver Testing
Metabolic dysfunction‑associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction‑associated steatohepatitis (MASH), affect millions and are linked to obesity, type 2 diabetes,... Read more