Serum-based biomarkers of pancreatic cancer and uses thereof for disease detection and diagnosis
Inventors
Pastural, Elodie • Ritchie, Shawn
Assignees
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Publication Number
US-10656155-B2
Publication Date
2020-05-19
Expiration Date
Abstract
Biomarkers of pancreatic cancer are described, as well as methods using these compounds for detecting pancreatic cancer. The methods can be used to diagnose a patient's health state, or change in health state, or for diagnosing risk of developing or the presence of pancreatic cancer. The method comprises analyzing a sample from a patient to obtain quantifying data for one or more than one of the metabolite markers; comparing the quantifying data to corresponding data obtained for one or more than one reference sample to identify abnormalities in the level of the metabolite marker(s) in the sample; and making a diagnosis if an abnormality is observed. Standards and kits for carrying out the method are also described.
Core Innovation
The invention relates to an analytical method for diagnosing pancreatic cancer in a patient by performing a mass spectrometry assay on at least one blood sample from the patient. The assay uses a Fourier transform ion cyclotron resonance, time of flight, magnetic sector, quadrupole or triple quadrupole mass spectrometer to obtain a collision induced dissociation (CID) MS/MS fragmentation pattern for one or more metabolite markers and obtain quantifying data for the one or more metabolite markers.
A result of the mass spectrometry assay is generated comprising at least the presence of a decrease in the level of the one or more metabolite marker(s) in the blood sample. This decrease is determined by comparing the quantifying data for the metabolite marker(s) to corresponding data obtained for one or more reference blood samples. The method assigns the patient as having pancreatic cancer based on the decrease in the level of the metabolite marker(s).
The one or more metabolite marker(s) are defined as one or more of lysophosphatidylcholine LysoPC 20:5, phosphatidylcholine having a molecular formula of C44H84NO8P or C46H82NO8P, sphingomyelin having a molecular formula of C39H79N2O6P, and a metabolite having the molecular formula of C36H64O5. Each metabolite is characterized by a CID MS/MS fragmentation pattern using N2 as collision gas, including specified daughter ions and ionization modes, and the specification also defines a combination of these metabolite markers.
Claims Coverage
The provided claim set includes one independent claim with dependent claims that refine the analytical method and the metabolite marker definitions. It covers two main inventive features: the diagnostic method and the defined metabolite marker set.
Diagnosing pancreatic cancer using CID MS/MS quantification compared to reference blood samples
Performing a mass spectrometry assay on at least one blood sample from a patient using a Fourier transform ion cyclotron resonance, time of flight, magnetic sector, quadrupole or triple quadrupole mass spectrometer to obtain a CID MS/MS fragmentation pattern for one or more metabolite marker(s) and obtain quantifying data, generating a result comprising at least the presence of a decrease in the level of the one or more metabolite marker(s) by comparison to corresponding data from reference blood samples, and assigning the patient as having pancreatic cancer based on the decrease in the level.
Specific metabolite marker set characterized by CID MS/MS daughter ions and ionization modes
Using one or more metabolite markers selected from lysophosphatidylcholine LysoPC 20:5, phosphatidylcholine (C44H84NO8P or C46H82NO8P), sphingomyelin (C39H79N2O6P), and a metabolite with molecular formula C36H64O5, wherein each is characterized by a CID MS/MS fragmentation pattern using N2 as collision gas and analyzed under specified ionization mode conditions with specified daughter ions, or using a combination thereof.
The core inventive concept is a pancreatic cancer diagnostic analytical method that relies on CID MS/MS fragmentation characterization and quantifying data for defined metabolite markers, with pancreatic cancer assignment based on decreased marker levels versus reference blood sample data.
Stated Advantages
Supports diagnosing pancreatic cancer using blood sample metabolite marker decrease relative to reference blood samples.
Documented Applications
Diagnosing pancreatic cancer in a patient using a mass spectrometry assay on a blood sample and a decreased level of one or more specified metabolite markers.
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