Methods of diagnosing proliferative disorders
Inventors
Baker, Matthew James • Abel, Peter • Lea, Robert William
Assignees
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Publication Number
US-10288615-B2
Publication Date
2019-05-14
Expiration Date
Abstract
The present invention relates to methods of diagnosing and/or prognosing proliferative disorders, especially brain cancers (e.g. gliomas). In particular, the present invention provides a means to conveniently detect malignant tumors merely by assaying or analyzing blood (particularly blood serum). Cytokines and/or angiogenesis factors in blood serum have been found to be surprisingly powerful at indicating the presence of brain cancers in a subject. Moreover, spectroscopic analysis, especially ATR-FTIR analysis, of a blood sample has been demonstrated to be surprisingly effective at producing a signature that can be correlated with the presence, extent, severity, or aggressiveness of malignant tumors in a subject.
Core Innovation
The invention provides a method of diagnosing and/or prognosing a proliferative disorder in a subject by performing spectroscopic analysis on a plasma or serum sample to produce a spectroscopic signature characteristic of the plasma or serum sample. The spectroscopic analysis is Attenuated Total Reflection FTIR (ATR-FTIR), in which the plasma or serum sample is applied to a surface of an ATR crystal and allowed to dry so that the ATR crystals support a dried film of the plasma or serum sample during IR analysis. The resulting spectroscopic signature is used as a characteristic signature for the diagnosis and/or prognosis.
The method derives diagnostic and prognostic information from the spectroscopic signature by correlating the obtained signature with pre-correlated signatures and/or using a predictive model. The correlation links the spectroscopic signature to favorable or unfavorable diagnosis and/or prognosis for the proliferative disorder, using a database of pre-correlated analyses and/or a trained predictive model to associate the signature with clinical outcomes.
The disclosed approach is applicable to proliferative disorders including brain cancer (glioma) and the presence, extent, severity, aggressiveness, and treatment responsiveness of a malignancy. The method further includes assaying a subject’s plasma or serum sample to measure one or more cytokines and/or angiogenesis factors as part of the overall diagnostic/prognostic framework, including IFN-γ, angiopoietin, follistatin, HGF, IL-8, leptin, PDGF-BB, and PECAM-1.
Claims Coverage
The independent claim covers diagnosing and/or prognosing a proliferative disorder using ATR-FTIR spectroscopic analysis of dried films formed on ATR crystals from plasma or serum samples, generating a characteristic spectroscopic signature. Four inventive features are set out in the claim set.
ATR-FTIR dried-film signature from plasma or serum
Performing spectroscopic analysis upon a plasma or serum sample to produce a spectroscopic signature characteristic of the plasma or serum sample, wherein the spectroscopic analysis is Attenuated Total Reflection FTIR (ATR-FTIR) in which the sample is applied to a surface of an ATR crystal and allowed to dry and the ATR crystals support a dried film of the plasma or serum sample during IR analysis.
Correlation to pre-correlated signatures and/or predictive model
Comparing a spectroscopically obtained signature to pre-correlated signatures in a database and/or using a trained predictive model to correlate the signature with a favorable or unfavorable diagnosis and/or prognosis.
Cytokine and/or angiogenesis factor assay of plasma or serum
Assaying a subject’s plasma or serum sample to measure one or more cytokines and/or angiogenesis factors.
Malignant versus benign brain cancer/proliferative disorder diagnosis
Determining whether a tumor is malignant or benign by diagnosing and/or prognosing a brain cancer or proliferative disorder according to claim 1.
Overall, the claim set centers on ATR-FTIR spectroscopic signatures generated from dried plasma or serum films on ATR crystals, and extends to correlating those signatures with pre-correlated signatures and/or a predictive model to support favorable or unfavorable diagnosis/prognosis. The dependent claims also optionally incorporate cytokine/angiogenesis factor measurements and narrow the clinical application toward malignant versus benign brain cancer/proliferative disorder.
Stated Advantages
Provides a method of diagnosing and/or prognosing a proliferative disorder in a subject using ATR-FTIR spectroscopic signatures from plasma or serum dried films on ATR crystals.
Supports correlation of spectroscopic signatures to favorable or unfavorable diagnosis and/or prognosis using pre-correlated signatures and/or a predictive model.
Supports clinical characterization of brain cancer (glioma) including presence, extent, severity, aggressiveness, and treatment responsiveness.
Uses cytokines and/or angiogenesis factors as biomarkers alongside ATR-FTIR spectroscopic signatures.
Documented Applications
Diagnosing and/or prognosing proliferative disorders, including brain cancer (glioma), using ATR-FTIR analysis of plasma or serum dried films and correlated spectroscopic signatures.
Determining whether a tumor is malignant or benign for a brain cancer/proliferative disorder.
Assessing presence, extent, severity, aggressiveness, and treatment responsiveness of a malignancy in brain cancer (glioma).
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