Analytically validated protein biomarkers of chronic pancreatitis and pancreatic cancer for potential clinical diagnosis with mass spectrometry

Chang, Chiz‐Tzung; Chen, Chao‐Jung

doi:10.1002/rcm.8580

Cited by 5 publications

(9 citation statements)

References 80 publications

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“…28 29 Those biomarkers analytically validated for diagnosis using mass spectrometry are reviewed by Chou et al, but diagnostic accuracy is mostly unknown. 30 Studies in rodents employing spontaneous and pharmacologically induced models of CP suggested significant alterations to the pancreatic metabolome, including energy production, anabolism, lipid synthesis and ROS detoxification pathways. 31 32 Small and due to their heterogeneity inconclusive nuclear MR-spectroscopy-based human studies identified changes in citrate and adenosine levels in urine and 33 34 This prompted us to conduct a trial with a study design more adequate for biomarker development.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects

Adam

Beyer

Christiansen³

et al. 2021

Gut

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ObjectiveChronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management.DesignWe conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines. A signature to distinguish CP from controls (n=160) was identified using gas chromatography-mass spectrometry and liquid chromatography‐tandem mass spectrometry on ethylenediaminetetraacetic acid (EDTA)-plasma and validated in independent cohorts.ResultsA Naive Bayes algorithm identified eight metabolites of six ontology classes. After algorithm training and computation of optimal cut-offs, classification according to the metabolic signature detected CP with an area under the curve (AUC) of 0.85 ((95% CI 0.79 to 0.91). External validation in two independent cohorts (total n=502) resulted in similar accuracy for detection of CP compared with non-pancreatic controls in EDTA-plasma (AUC 0.85 (95% CI 0.81 to 0.89)) and serum (AUC 0.87 (95% CI 0.81 to 0.95)).ConclusionsThis is the first study that identifies and independently validates a metabolomic signature in plasma and serum for the diagnosis of CP in large, prospective cohorts. The results could provide the basis for the development of the first routine laboratory test for CP.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects

Adam

Beyer

Christiansen³

et al. 2021

Gut

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“…Much of the development work has focused on MS instrumentation and techniques. − Additionally, developments in liquid chromatography (LC) have enabled complex mixture analysis. − This has led to the wide-scale adoption of LC-MS techniques by the scientific community for the study of human disease. Indeed, LC-MS ‘omics methods have been broadly utilized to investigate conditions such as cardiovascular disease, − cancer, − diabetes, ,− and neurodegenerative disorders. − …”

Section: Introductionmentioning

confidence: 99%

Combining Field-Enabled Capillary Vibrating Sharp-Edge Spray Ionization with Microflow Liquid Chromatography and Mass Spectrometry to Enhance ‘Omics Analyses

Majuta

DeBastiani

et al. 2021

J. Am. Soc. Mass Spectrom.

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Field-enabled capillary vibrating sharp-edge spray ionization (cVSSI) has been combined with high-flow liquid chromatography (LC) and mass spectrometry (MS) to establish current ionization capabilities for metabolomics and proteomics investigations. Comparisons are made between experiments employing cVSSI and a heated electrospray ionization probe representing the state-of-the-art in microflow LC-MS methods for 'omics studies. For metabolomics standards, cVSSI is shown to provide an ionization enhancement by factors of 4 ± 2 for both negative and positive ion mode analyses. For chymotryptic peptides, cVSSI is shown to provide an ionization enhancement by factors of 5 ± 2 and 2 ± 1 for negative and positive ion mode analyses, respectively. Slightly broader high-performance liquid chromatography peaks are observed in the cVSSI datasets, and several studies suggest that this results from a slightly decreased post-split flow rate. This may result from partial obstruction of the pulled-tip emitter over time. Such a challenge can be remedied with the use of LC pumps that operate in the 10 to 100 μL•min −1 flow regime. At this early stage, the proof-of-principle studies already show ion signal advantages over stateof-the-art electrospray ionization (ESI) for a wide variety of analytes in both positive and negative ion mode. Overall, this represents a ∼20−50-fold improvement over the first demonstration of LC-MS analyses by voltage-free cVSSI. Separate comparisons of the ion abundances of compounds eluting under identical solvent conditions reveal ionization efficiency differences between cVSSI and ESI and may suggest varied contributions to ionization from different physicochemical properties of the compounds. Future investigations of parameters that could further increase ionization gains in negative and positive ion mode analyses with the use of cVSSI are briefly presented.

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“…Direct markers of pancreatic exocrine function are invasive because they involve obtaining pancreatic juices via endoscopy or Dreiling tube following stimulation by secretin or cholecystokinin. Bicarbonate, lipase, or trypsin is then measured, and these measurements are highly sensitive for late CP but have a lower sensitivity range of 70-75% for early chronic pancreatitis [25]. Indirect markers, on the other hand, are non-invasive tests of pancreatic insufficiency.…”

Section: Discussionmentioning

confidence: 99%

“…Indirect markers, on the other hand, are non-invasive tests of pancreatic insufficiency. One example is faecal elastase-1, with a cutoff of 100 micrograms having a sensitivity of 46.5% and a specificity of 88% for the diagnosis of CP [25]. Early biomarkers for CP include chemokines like transforming growth factor-Beta 1 (TGF-β1), platelet-derived growth factor BB, and chemerin, which are elevated in CP [25].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Differentiation between Pancreatitis and Pancreatic Cancer: A Scoping Review

Madela,

Ferndale,

Aldous

2024

Diagnostics

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Pancreatitis, encompassing acute and chronic forms, and pancreatic cancer pose significant challenges to the exocrine tissue of the pancreas. Recurrence rates and complications following acute pancreatitis episodes can lead to long-term risks, including diabetes mellitus. Chronic pancreatitis can develop in approximately 15% of cases, regardless of the initial episode’s severity. Alcohol-induced pancreatitis, idiopathic causes, cigarette smoking, and hereditary pancreatitis contribute to the progression to chronic pancreatitis. Chronic pancreatitis is associated with an increased risk of pancreatic cancer, with older age at onset and smoking identified as risk factors. This scoping review aims to synthesise recent publications (2017–2022) on the diagnostic differentiation between pancreatitis and pancreatic cancer while identifying knowledge gaps in the field. The review focuses on biomarkers and imaging techniques in individuals with pancreatitis and pancreatic cancer. Promising biomarkers such as faecal elastase-1 and specific chemokines offer non-invasive ways to assess pancreatic insufficiency and detect early biomarkers for chronic pancreatitis. Imaging techniques, including computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), and positron emission tomography (PET), aid in differentiating between chronic pancreatitis and pancreatic cancer. However, accurately distinguishing between the two conditions remains a challenge, particularly when a mass is present in the head of the pancreas. Several knowledge gaps persist despite advancements in understanding the association between pancreatitis and pancreatic cancer, including the correlation between histopathological grading systems, non-invasive imaging techniques, and biomarkers in chronic pancreatitis to determine the risk of progression to pancreatic cancer, as well as differentiating between the two conditions. Further research is necessary to enhance our understanding of these aspects, which can ultimately improve the diagnosis and management of pancreatitis and pancreatic cancer.

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Analytically validated protein biomarkers of chronic pancreatitis and pancreatic cancer for potential clinical diagnosis with mass spectrometry

Cited by 5 publications

References 80 publications

Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects

Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects

Combining Field-Enabled Capillary Vibrating Sharp-Edge Spray Ionization with Microflow Liquid Chromatography and Mass Spectrometry to Enhance ‘Omics Analyses

Diagnostic Differentiation between Pancreatitis and Pancreatic Cancer: A Scoping Review

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