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US 12,618,843 B2Granted
Biomarker combinations for determining aggressive prostate cancer
AssigneeMinomic International Ltd.
InventorsDouglas Campbell, Thao Ho-Le, Brad Walsh, Rachel Levin
Life of this patent
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Abstract
The present invention provides methods for the diagnosis of aggressive prostate cancer, including, but not limited to, methods for discerning between aggressive and non-aggressive forms of prostate cancer, and methods for detecting aggressive prostate cancer based on comparisons to a mixed control population of subjects with non-aggressive prostate cancer or not having prostate cancer.
Claims20
A method for diagnosing aggressive prostate cancer (CaP) in a test subject, comprising:
- (a) detecting one or more analyte/s in a biological sample from the test subject to thereby obtain an analyte level for each said analyte in the test subject's biological sample, and obtaining a measurement of two or more clinical variables from the test subject;
- and
- (b) applying a suitable algorithm and/or transformation to a combination of the clinical variable measurements and analyte level/s of the test subject to thereby generate a test subject score value for comparison to a threshold value;
- (c) determining that the test subject has aggressive CaP when the subject test score value is above the threshold value;
- and
- (d) treating the subject diagnosed with aggressive CaP with one or more of surgery, radiation, or drugs,
- wherein:
- the one or more analyte/s comprise or consist of leptin,
- the two or more clinical variables comprise at least two of:
- total prostate-specific antigen (PSA), digital rectal examination (DRE), subject age, prostate volume, and
- the threshold value is determined by:
- detecting said one or more analyte/s in a series of biological samples obtained from a population of subjects having aggressive CaP and from a population of control subjects not having aggressive CaP, to thereby obtain an analyte level for each said analyte in each said biological sample of the series;
- combining each of said one or more analyte levels of the series with measurements of said two or more clinical variables obtained from each said subject from the population of subjects having aggressive CaP and from each subject from the population of control subjects, in a manner that allows discrimination between aggressive CaP and an absence of aggressive CaP, to thereby generate the threshold value;
- and wherein the two or more clinical variables and the one or more analyte/s comprise any one of the following:
- total PSA, prostate volume, leptin, subject age, IL-7 and VEGF;
- total PSA, prostate volume, leptin, subject age, IL-7, VEGF, osteopontin and CD40L;
- total PSA, % free PSA, prostate volume, leptin, osteopontin and HE4.WFDC2;
- total PSA, DRE, leptin, subject age, VEGF and IL-7;
- total PSA, DRE, leptin, subject age, VEGF, osteopontin;
- total PSA, DRE, leptin, subject age, VEGF, IL-7, GPC-1;
- total PSA, DRE, leptin, subject age, VEGF, osteopontin, GPC-1;
- total PSA, DRE, leptin, subject age, VEGF, IL-7, GPC-1, % free PSA;
- total PSA, DRE, leptin, subject age, VEGF, osteopontin, GPC-1, % free PSA;
- total PSA, DRE, leptin, subject age, prior negative biopsy, VEGF-C, osteopontin, GPC-1, CD40L, proPSA, % free PSA.
21 more elements
A method for discerning whether a test subject has non-aggressive or aggressive prostate cancer (CaP), comprising:
- (a) detecting one or more analyte/s in a biological sample from the test subject to thereby obtain an analyte level for each said analyte in the test subject's biological sample, and obtaining a measurement of two or more clinical variable/s from the test subject;
- and
- (b) applying a suitable algorithm and/or transformation to a combination of the clinical variable measurements and analyte level/s to thereby generate a test subject score value for comparison to a threshold value;
- (c) determining that the test subject has aggressive CaP when the subject test score value is above the threshold value or determining that the test subject has non-aggressive CaP when the subject test score value is below the threshold value;
- and
- (d) treating the subject diagnosed with aggressive CaP with one or more of surgery, radiation, or drugs,
- wherein
- the test subject has previously been determined to have prostate cancer or a likelihood of having prostate cancer (e.g. by any one or more of a PSA-based test, digital rectal examination (DRE), family history, an ultrasound-based test, magnetic resonance imaging (MRI), a urine biomarker test, an exosome-based test),
- the one or more analyte/s comprise or consist of leptin,
- the two or more clinical variables comprise at least two of:
- total PSA, DRE, subject age, prostate volume, and
- the threshold value is determined by:
- detecting said one or more analyte/s in a series of biological samples obtained from a population of subjects having aggressive CaP and from a population of control subjects having non-aggressive CaP, to thereby obtain an analyte level for each said analyte in each said biological sample of the series;
- combining each of said one or more analyte levels of the series with measurements of said two or more clinical variables obtained from each subject from the population of subjects having aggressive CaP and from each subject from the population of control subjects, to thereby generate the threshold value;
- and wherein the two or more clinical variables and the one or more analyte/s comprise any one of the following:
- total PSA, prostate volume, leptin, subject age, IL-7 and VEGE;
- total PSA, prostate volume, leptin, subject age, IL-7, VEGF, osteopontin and CD40L;
- total PSA, % free PSA, prostate volume, leptin, osteopontin and HE4.WFDC2;
- total PSA, DRE, leptin, subject age, VEGF and IL-7;
- total PSA, DRE, leptin, subject age, VEGF, osteopontin;
- total PSA, DRE, leptin, subject age, VEGF, IL-7, GPC-1;
- total PSA, DRE, leptin, subject age, VEGF, osteopontin, GPC-1;
- total PSA, DRE, leptin, subject age, VEGF, IL-7, GPC-1, % free PSA;
- total PSA, DRE, leptin, subject age, VEGF, osteopontin, GPC-1, % free PSA;
- total PSA, DRE, leptin, subject age, prior negative biopsy, VEGF-C, osteopontin, GPC-1, CD40L, proPSA, % free PSA.
22 more elements
Dependencies are inferred from the claim text.