Methods of detecting prostate cancer
Inventors
Kassis, Amin I. • Stylli, Harry • Kelly, Colleen • Erickson, Geoffrey • Wojno, Kirk J.
Assignees
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Publication Number
US-12181477-B2
Publication Date
2024-12-31
Expiration Date
Abstract
The invention described herein provides biological markers for the diagnosis, prognosis, and monitoring of prostate cancer
Core Innovation
The invention relates to methods of measuring levels of prostate cancer-specific biological markers in subject samples by analyzing phagocytic cells and non-phagocytic cells from the same subject. In the approach, marker levels are measured in subject macrophage cells and in subject non-phagocytic cells, with the measurement performed prior to the subject receiving treatment for prostate cancer. The marker panel includes five or more markers comprising ALPL, PI3, CXCR2, GPR97, and MMP9.
The biological markers are measured as gene expression levels, protein expression levels, and/or protein activity levels, and differences in the measured levels are used to indicate prostate cancer. Marker differences, including fold-change thresholds, distinguish prostate cancer from non-cancer contexts, with reported sensitivity and specificity supporting the marker signatures.
The disclosure includes gene signature sets for macrophage and neutrophil contexts, including PC-MACRO 1-4 and PC-NEUTRO 1-11, and describes a microarray-based discovery and validation workflow using cross-validation and differential gene expression comparisons. The disclosure also supports evaluating treatment efficacy or testing candidate compounds by monitoring changes in marker levels, and includes related kit concepts for measuring marker panels.
Claims Coverage
The independent claim is directed to a prostate cancer diagnostic/assessment method based on measuring a defined set of five or more markers in macrophage cells and in non-phagocytic cells from the same subject prior to treatment. Dependent claims refine how the marker levels are measured, which non-phagocytic cell types are encompassed, and the timing relationship relative to treatment, including a second time point.
Measuring a defined multi-marker panel in subject macrophage and non-phagocytic cells before prostate cancer treatment
Measuring the levels of five or more markers comprising ALPL, PI3, CXCR2, GPR97, and MMP9 in a population of the subject's macrophage cells and measuring the levels of the five or more markers in a population of the subject's non-phagocytic cells, wherein measuring levels occurs prior to the subject receiving treatment for prostate cancer.
Measuring marker levels as gene expression levels
Measuring the marker levels as gene expression levels.
Determining gene expression levels using a selected sequencing technique
Measuring gene expression levels using a sequencing technique selected from a group including direct sequencing, RNA sequencing, whole transcriptome shotgun sequencing, random shotgun sequencing, Sanger dideoxy termination sequencing, whole-genome sequencing, sequencing by hybridization, pyrosequencing, capillary electrophoresis, gel electrophoresis, duplex sequencing, cycle sequencing, single-base extension sequencing, solid-phase sequencing, high-throughput sequencing, massively parallel signature sequencing, emulsion PCR, sequencing by reversible dye terminator, paired-end sequencing, near-term sequencing, exonuclease sequencing, sequencing by ligation, short-read sequencing, single-molecule sequencing, sequencing-by-synthesis, real-time sequencing, reverse-terminator sequencing, nanopore sequencing, 454 sequencing, Solexa Genome Analyzer sequencing, MS-PET sequencing, and mass spectrometry; and combinations thereof.
Defining non-phagocytic cells as T cells, B cells, null cells, basophils, or mixtures
Using non-phagocytic cells selected as T cells, B cells, null cells, basophils, or mixtures thereof.
Including a second time point after prostate cancer treatment
Measuring at a second time point that occurs after the subject receives treatment for prostate cancer.
Across the independent claim and its dependents, the core coverage centers on a pre-treatment measurement workflow that quantifies a specified multi-marker panel in macrophage versus non-phagocytic cells, with further definition of gene expression measurement, explicit non-phagocytic cell types, and an optional post-treatment second time point.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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