- It is intended for research use only
- The kit consists of 3 assays
- The Kidney Cancer Assay 1 measures human ApoA2 and CRP in serum and plasma
- The Kidney Cancer Assay 2 measures human CD117 in serum and plasma
- The Kidney Cancer Assay 3 measures human Fibronectin in serum and plasma
- Additional sample types may be suitable but have not been validated
- The total assay time is less than 1.5 hours
- Components of the kit are provided ready to use, concentrated or lyophilized
Apolipoprotein A-II (ApoA2) belongs to the family of apolipoproteins and it is the second most abundant protein of the high density lipoprotein (HDL) particles. The protein is found in plasma as a monomer, homodimer, or heterodimer with apolipoprotein D. It may also stabilize HDL structure by its association with lipids, and affect the HDL metabolism.
Defects in this gene may result in apolipoprotein A-II deficiency or hypercholesterolemia. Although some studies have found an overexpression of ApoA2 in hypertriglyceridemic, obese and insulin-resistant subjects, another research adds that ApoA-II is associated with a decreased risk of future coronary artery disease in apparently healthy people, its role in humans is still controversial.
The -256C > T polymorphism in the ApoA2 gene promoter is one of the most studied, and CC genotype has been associated with increased Body Mass Index (BMI) or obesity in different populations. This polymorphism also influences other cardiovascular risk factors such as the ratio ApoA1/ApoA2 or the development of atherosclerosis. There were also observed the lipoprotein changes in the human apoA-II transgenic mice on a regular chow diet.
ApoA2 is probably a differential protein of hepatocellular carcinoma (HCC) and maybe related to the pathogenesis of HCC.
C-Reactive Protein (CRP) belongs to the pentraxin family of calciumdependent ligand-binding plasma proteins, the other member of which in humans is serum amyloid P component (SAP). Human CRP physiologically binds with highest affinity to phosphocholine residues, but it also binds to a variety of other autologous and extrinsic ligands, and it aggregates or precipitates the cellular, particulate, or molecular structures bearing these ligands. It was the first acute-phase protein to be described and it is a sensitive systemic marker of inflammation and tissue damage. The human CRP molecule (Mr 115,135) is composed of five identical nonglycosylated polypeptide subunits.
However, surprisingly in view of the sensitivity, speed, and range of the CRP response, subjects in the general population tend to have stable CRP concentrations characteristic for each individual, apart from occasional spikes presumably related to minor or subclinical infections, inflammation, or trauma.
CRP responses in infections (bacterial systemic/severe fungal, mycobacterial, viral), allergic complications of infection (Rheumatic fever), inflammation disease (Rheumatoid arthritis, Juvenile chronic arthritis, Psoriatic arthritis, Systemic vasculitis, Crohn disease), necrosis (myocardial infarction, acute pancreatitis), trauma (surgery, burns, fractures), malignancy (lymphoma, carcinoma, sarcoma) and others. Elevated CRP has been alsp associated with several malignancies in addition to a worse prognosis for those malignancies. CRP correlate with melanoma disease progression.
CD117 (KIT), encoded by the proto-oncogene c-kit, is a transmembrane protein belonging to the type III subfamily of the receptor tyrosine kinases. It has extracellular, intramembranous and intracellular domains. Normally KIT is activated (phosphorylated) by binding of its ligand, the stem cell factor (SCF). This leads to a phosphorylation cascade ultimately activating various transcription factors in different cell types. Such activation regulates cellular activities as apoptosis, cell differentiation, proliferation, chemotaxis, and cell adhesion.
Expression of CD117 has been described in numerous normal cells, including haematopoietic cells, germ cells, mast cells, melanocytes, breast epithelial cells, Cajal cells of the gastrointestinal tract. CD117 have been identi¬fied as a key oncogenic driver in a variety of tumors including mast cell leukemia, Ewing sarcoma, neuroblastoma, melanoma, thyroid, endometrial, ovarian and breast cancers. CD117 positivity has been variably reported in sarcomas. It is also expressed in pulmonary and other small cell carcinomas, adenoid cystic carcinoma, renal chromophobe carcinoma, thymic, and some ovarian and few breast carcinomas.
Recently, CD117, as a biomarker of prognosis in malignancies, has generated much interest. But the conclusions for its prognostic value are controversial. In gastrointestinal stromal tumors, myeloid leukemias and mast cell disorders, for example, c-KIT gene gain-of-function muta¬tions result in constitutive tyrosine kinase activ¬ity and are considered to play a central role in oncogenesis and sustained tumor growth. On the other hand, a markedly better outcome has already been demonstrated in tumors that expressed c-KIT com¬pared with those that did not, such as nasopharyn¬geal carcinomas and multiple myeloma.
CD117 expression may be a useful prognostic marker for identifying an aggressive molecular subgroup of oesophageal squamous cell carcinoma with extremely poor clinical outcome, and may serve as an attractive therapeutic target.
Interestingly, pooled analysis exhibited a significant correlation between CD117 expression and poor overall survival of patients with osteosarcoma and renal carcino¬ma, suggesting that CD117 might be an inde¬pendent prognostic factor of poor survival in these patients. Notably, CD117 is a positive diagnostic marker of gastrointestinal stromal tumor (GIST), and is widely used in oncology treatment guidelines. CD117 tyrosine kinase inhibitors such as imatinib mesylate are the generally accepted treatment of metastatic GISTs.
CD117 deficiency due to hereditary nonsense/missense mutations leads to disruption of KIT-dependent functions such as erythropoiesis, skin pigmentation, fertility, and gastrointestinal motility. Conversely, pathologic activation through gain-of-function mutations leads to neoplasia of CD117-dependent and CD117-positive cell types.
Fibronectins (FN) are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. In vivo, fibronectins are found in body fluids (300 ug/ml in plasma, less amounts in other fluids), soft connective tissue matrices, and most basement membranes. Fibronectins are synthesized by a wide variety of cells in vitro, fibroblasts and endothelial cells are major producers, but many other cell types, including some epithelial cells, synthesize fibronectin at lower levels.
Generally, the functional protein is composed of two similar, but not always identical subunits of 220 to 250 kDa that are joined by disulphide bonds at the carboxyl-termini to create the characteristic fibronectin dimer. Each monomer consists of three types of repeating units: type I, type II and type III. FN contains 12 type I repeats, two type II repeats and 15-17 type III repeats, which together account for approximately 90% of the FN sequence.
Fibronectin (FN) mediates a wide variety of cellular interactions with the extracellular matrix (ECM) and plays important roles in cell adhesion, migration, growth and differentiation, proliferation and oncogenic transformation, survival, cytoskeletal organization, phagocytosis, and hemostasis.
Two classes of fibronectin exist in vivo, each discovered through widely different research initiatives. Plasma fibronectin (pFn) was first identified and it is found primarily as a soluble dimer circulating in various body fluids. The search for tumor markers led to the discovery of cellular fibronectin (cFn) described then as“galactoprotein”, and later determined to be the “surface fibroblast antigen”. This fibronectin is found predominantly as an insoluble, multimeric, fibrillar constituent of extracellular matrices. Both major forms, pFn and cFn, exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. This elevated presence has also been associated with various chronic disorders that are characterized by extensive tissue damage.
FN is widely expressed by multiple cell types and is critically important in vertebrate development, as demonstrated by the early embryonic lethality of mice with targeted inactivation of the FN gene. Fibronectin is ubiquitously expressed in the extracellular matrix, and experimental evidence has shown that it modulates blood vessel formation. Using transgenic mouse was established that circulating fibronectin facilitates the growth of bone metastases by enhancing blood vessel formation and maturation.
Cellular fibronectin plays a critical role in tissue-specific morphogenesis and cellular differentiation during embryonic development. Other reports highlight the chemotactic activity of cFn and its regulation of growth factors during active wound repair
Circulating fibronectin enhances its local production in tumors through a positive feedback loop and increases the amount of vascular endothelial growth factor (VEGF) retained in the matrix. Both fibronectin and VEGF then cooperate to stimulate blood vessel formation. Fibronectin content in the tumor correlates with the number of blood vessels and tumor growth in the mouse models. So fibronectin could serve as a prognostic biomarker for breast and prostate cancers and possibly other cancers.
Clinical use and areas of investigation:
Clinical use and areas of investigation :
- Kidney cancer
- Breast cancer
- Lipid metabolism
- Inflammations and Infections
- Cardiovascular disease
- Cell differentiation
- Blood vessel development