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-10024857-B2
Publication Date
2018-07-17
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 provides an analytical method for diagnosing pancreatic cancer in a patient by performing a mass spectrometry assay on at least one blood sample. The method uses one or more specified mass spectrometer types to obtain a collision induced dissociation (CID) MS/MS fragmentation pattern for one or more metabolite markers and to obtain quantifying data for the metabolite marker(s).
A result of the mass spectrometry assay is generated by comparing the quantifying data for the metabolite marker(s) to corresponding data obtained from one or more reference blood samples. The result includes at least the presence or absence of a decrease in the level of the one or more metabolite markers, and the patient is assigned as having or not having pancreatic cancer, where a decrease indicates the presence of pancreatic cancer.
The method is further directed to embodiments in which the blood sample is blood serum and the reference blood sample is from one or more pancreatic cancer-negative humans. Quantifying data can be based on internal standard molecules and ratio-based comparison, and metabolite profiling can be refined by liquid/liquid extraction with non-polar metabolites dissolved in an organic solvent and polar metabolites dissolved in an aqueous solvent.
The metabolite marker is at least a metabolite having the molecular formula C36H66O6, characterized by a CID MS/MS fragmentation pattern using N2 as collision gas and analyzed under negative ionization, including a specified set of daughter ions. The disclosed work also refers to a defined metabolite marker set with associated molecular formulas and CID MS/MS fragmentation daughter-ion patterns.
Claims Coverage
The claim set covers a comparison-based pancreatic cancer diagnostic using CID MS/MS metabolite-marker quantification relative to reference blood samples, with assignment based on decreased marker levels. It includes at least one specific metabolite marker defined by molecular formula and N2 CID daughter ions under negative ionization, plus dependent refinements for specimen type, reference source, internal-standard ratio comparison, liquid/liquid extraction, and a defined marker panel.
Comparison-based CID MS/MS metabolite-marker decrease diagnosis
Performing a mass spectrometry assay on at least one blood sample using a specified mass spectrometer to obtain CID MS/MS fragmentation patterns for one or more metabolite markers and obtain quantifying data, generating a result indicating presence or absence of a decrease in the metabolite marker level by comparing to corresponding data from one or more reference blood samples, and assigning the patient as having or not having pancreatic cancer, wherein a decrease indicates pancreatic cancer.
CID MS/MS characterized metabolite marker with C36H66O6 daughter-ion set
Using at least a metabolite marker that is a metabolite having molecular formula C36H66O6, characterized by a CID MS/MS fragmentation pattern using N2 as collision gas and analyzed under negative ionization comprising specified daughter ions.
Internal standard molecule ratio comparison
Quantifying the metabolite markers using one or more internal standard molecules, calculating ratios of each metabolite marker level to an internal standard level, and generating the result by comparing each ratio to corresponding ratios from one or more reference samples.
Liquid/liquid extraction partitioning of non-polar and polar metabolites
Performing a liquid/liquid extraction on the blood sample such that non-polar metabolites are dissolved in an organic solvent and polar metabolites are dissolved in an aqueous solvent.
Reference samples from pancreatic cancer-negative humans
Using reference blood samples from one or more pancreatic cancer-negative humans.
Blood serum specimen
Performing the method using a blood serum sample.
Defined metabolite marker panel with specified CID daughter-ion patterns
Using a metabolite marker set that includes at least a defined number of specified metabolite markers with associated molecular formulas and CID MS/MS fragmentation daughter-ion patterns using N2 as collision gas, with ionization modes specified for those patterns.
Overall, the claims cover a CID MS/MS-based diagnostic framework that assigns pancreatic cancer based on decreased levels of metabolite marker(s) compared to reference blood samples. Dependent claims further refine blood serum use, reference-source constraints, ratio-based internal-standard quantification, liquid/liquid extraction partitioning, and a defined metabolite marker panel with specified CID daughter-ion patterns.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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