Bladder cancer detection composition, kit and associated methods
Inventors
Goodison, Steven • Rosser, Charles J.
Assignees
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Publication Number
US-9249467-B2
Publication Date
2016-02-02
Expiration Date
Abstract
Compositions, kits, and methods for the diagnosis, prognosis, and monitoring of bladder cancer in a subject are provided by detecting in a urine sample a combination of biomarkers. In one embodiment of the invention, a nine-biomarker panel consisting of IL-8, MMP9, SDC1, CCL18, SERPINE1, CD44, VEGF-A, CA9, and ANG may be detected. In another embodiment of the invention, a three-biomarker panel consisting of CCL18, CD44, and VEGF-A may be detected. In yet another embodiment of the invention, a nine-biomarker panel consisting of CA9, CCL18, MMP12, TMEM45A, MMP9, SEMA3D, ERBB2, CRH, and MXRA8 may be detected.
Core Innovation
The invention relates to bladder-cancer detection compositions, kits, and methods based on measuring biomarker overexpression in urine. A urine sample from a subject is contacted with a panel of antibodies, and the presence and quantity of protein-antibody complexes are detected.
In an antibody-panel embodiment, the panel consists of antibodies that bind to and form a complex with each of Interleukin-8 (IL8), Angiogenin (ANG), Plasminogen activator inhibitor 1 (PAI1), Matrix metallopeptidase 10 (MMP10), and Apolipoprotein E (APOE), with the panel optionally including further antibodies that bind to and form a complex with each of CA9, SDC1, MMP9 and VEGFA.
Supporting evidence described in the document includes gene-expression signature development using urine-derived urothelial cells and reporting high diagnostic performance for a constrained 9-gene transcriptional classifier and a 14-gene diagnostic signature, along with protein/ELISA urine analysis of candidate markers such as IL-8, MMP9, SDC1, CCL18, SERPINE1, CD44, VEGF-A, CA9 and ANG. Multivariate performance is described for a combined 9-biomarker assay and strong performance for reduced biomarker panels including reduced panels such as CCL18/VEGF-A and CCL18/CD44/VEGF-A.
Claims Coverage
The document includes one independent method claim. It is centered on detecting and quantifying protein-antibody complexes in urine using a defined antibody panel targeting specified proteins, with optional inclusion of additional antibody targets.
Urine antibody panel for targeted protein-antibody complexes
Obtaining a urine sample from a subject; contacting the urine sample with a panel of antibodies in which the panel consists of antibodies that bind to and form a complex with each of IL8, ANG, PAI1, MMP10, and APOE, and optionally further comprises antibodies that bind to and form a complex with each of CA9, SDC1, MMP9 and VEGFA; and detecting the presence and quantity of the protein-antibody complexes in the biological sample.
Overall claim coverage is directed to a urine-based immunoassay approach that detects and quantifies antibody-bound complexes for a defined set of bladder-cancer associated proteins, optionally expanded with additional targets.
Stated Advantages
Documented Applications
Bladder-cancer detection using urine samples by measuring biomarker overexpression and detecting protein-antibody complexes formed by an antibody panel targeting specified proteins.
Detection, prognosis, and monitoring are described as use cases in connection with nucleic acid or protein detection formats (including ELISA and binding-complex detection) and associated urine normalization and thresholds.
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