Reference
Biomarker discovery and validation
Biomarker discovery and validation
Biomarker discovery is a hot research topic. In actuality, this kind of research is much more common than you might think. In fact, you may be doing biomarker research right now, even if you do not think of it as such. In this article, we discuss various types of biomarker discovery methods used with RayBiotech Antibody Arrays.
Biomarker Discovery with Antibody Arrays Biomarkers are surrogate markers, including DNA, RNA, proteins, metabolites or imaging results, that reflect the presence or progression of disease or the effects of treatment. Traditional methods for biomarker discovery are almost exclusively based on mass spectrometry, an approach with many advantages and limitations. (
Kiehntopf, et al. Clin Chem Lab Med. 2007).
However, more recently multiplex antibody arrays have been used to screen for biomarkers. (
Borrebaeck & Wingren. Expert Rev Mol Diagnost. 2007). The advantages of such an approach are 1) protein biomarker hits are readily identified by the specificity of the antibody detecting it; 2) ELISA kits and antibodies are immediately available for validation; 3) much higher throughput; and 4) greater cost effectiveness.
Biomarkers can be indicative of the presence of disease (diagnostic), the disease process (mechanistic), likely disease progression (prognostic) or response to treatment (therapeutic). Presented below are examples of all of these types of biomarker discovery using RayBiotech Antibody Arrays.
Diagnostic BiomarkersThe best example of finding diagnostic biomarkers using antibody array technology is that for Alzhemer's (
Ray, et al. Nature Med. 2007). This publication is notable not just for its findings, but in the
details of the methods employed in the supplements. In this study, researchers at Stanford and Satoris, Inc., screened plasma samples from patients with Alzheimer's versus those with other forms of dementia and normal controls using our Human C-1000 arrays. Results of this training set was used to predict whether samples taken from test sets fit the pattern found in the training set. By doing so, they found a set of 18 biomarkers differentially expressed in Alzheimer's patients. RayBiotech and Satoris are currently working on a quantitative array based upon detecting these markers for release later this year (
RB-Satoris Press Release).
Plasma is not the only sample type used for finding biomarkers. Another group at the Mayo clinic also used our C-1000 arrays to discover several markers for asthma in sputum (
Kim, et al. Chest. 2009) Other groups have used our arrays to search for diagnostic biomarkers in urine (
Liu, et al. Am J Nephrol.2006.) and tears (
Sack, et al. Exper Eye Res. 2007.)
Mechanistic (Key Factor) BiomarkersPatient body fluids are not the only means for discovering disease related biomarkers. For example, investigation of the inflammatory cytokine profile uncovered a number of chemokines and inflammatory markers differentially secreted by chondrocytes from patients with arthritis versus normal controls (
De Ceuninck, et al. BBRC. 2004). Another group looked at differences in cytokine expression from airway epithelial cells due to chronic obstructive pulmonary disease (COPD), identifying adiponectin and its receptor as being potential key factors in this disease (
Miller, et al. J Immunol. 2009).
In vitro studies like these can identify key factors that may lead to understanding of the disease process as well as identification of potential diagnostic markers.
Prognostic and Therapeutic BiomarkersThe goal of personalized medicine is giving the right drug for the right indication to the right patient at the right time. Protein biomarkers in serum and other body fluids might provide prognostic information about the likelihood for a patient to respond to a given treatment. Also, disease progression for patients with the same disease can vary widely. Biomarkers indicative of the likely disease progression could be helpful, particulary in patients with cancer (
Ludwig & Weinstein. Nature Rev Cancer. 2005).
Here again, investigators have used antibody arrays to look for prognostic markers. Screening of serum from patients with stage IV melanoma using RayBiotech antibody arrays revealed that serum angiogenin concentrations predict patient response to treatment (
Vehinen, et al. Clin Exper Metastasis. 2006).
Also using our antibody arrays, researchers at Hoag Cancer Center found that baseline serum TARC/CCL17 levels were identified as a prognostic marker for response to a particular treatment for advanced melanoma (
Cornforth, et al. J Clin Immunol. 2009).
As with diagnostic markers, finding prognostic or therapeutic biomarkers may start with an in vitro experiment rather than looking at patient outcome. In one study, a group from Scripps Research Institute and University College Dublin examined changes in the cytokine secretion profiles of platelets treated with aspirin (
Coppinger, et al. Blood. 2007). Another group used our arrays to examine changes in the cytokine secretion profiles in response to PPAR agonists in adipocytes (
Klimcakova, et al. BBRC. 2007).
Surrogate markers of drug responsiveness in vitro could potentially provide evidence of drug efficacy in vivo, independent of patient symptoms. These surrogate markers could then be used to evaluate drug efficacy in clinical trials or to monitor patient progress in clinical treatment.
Antibody array technology presents a new paradigm in biomarker discovery. Arrays allow screening for dozens to literally hundreds of proteins simultaneously, accelerating biomarker research at a fraction of the cost of mass spectrometry.
