The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention.
IGFBP7 (human precursor Swiss Prot entry Q16270) is a secreted protein which is involved in regulation of of insulin-like growth factor expression in tissue and which modulates IGF binding to its receptors. It also reportedly stimulates prostacyclin production and cell adhesion. IGFBP7 suppresses growth and colony formation of prostate and breast cancer cell lines through an IGF independent mechanism, which causes a delay in the G1 phase of the cell cycle, and increased apoptosis. IGFBP7 is expressed in a wide range of normal human tissues and it usually shows reduced expression in cancer cell lines of prostate, breast, colon, and lung origin.
In addition, WO2011/097539 and WO2011/075744, each of which is hereby incorporated by reference in its entirety including all tables, figures and claims, describe the use of IGFBP7 for evaluating the renal status of a subject both individually and in multimarker panels. In particular, IGFBP7 levels measured by immunoassay are shown to correlate to risk stratification, diagnosis, staging, prognosis, classifying and monitoring of the renal status.
Signals obtained from specific binding assays such as immunoassays are a direct result of complexes formed between one or more binding species (e.g., antibodies) and the target biomolecule (i.e., the analyte) and polypeptides containing the necessary epitope(s) to which the antibodies bind. Immunoassays are often able to “detect” an analyte; but because an antibody epitope is on the order of 8 amino acids, an immunoassay configured to detect a marker of interest will also detect polypeptides related to the marker sequence, so long as those polypeptides contain the epitope(s) necessary to bind to the antibody or antibodies used in the assay. While such assays may detect the full length biomarker and the assay result be expressed as a concentration of a biomarker of interest, the signal from the assay is actually a result of all such “immunoreactive” polypeptides present in the sample. Such binding assays may also detect immunoreactive polypeptides present in a biological sample that are complexed to additional species, such as binding proteins, receptors, heparin, lipids, sugars, etc., provided that those additional species do not interfere in binding between the binding species and the target biomolecule. Typically, however, specific binding assays are formulated using purified analyte, and complex formation and fragmentation patterns are not considered. This is particularly true where the identity of such additional binding species are unknown.