By OMAR FORD
Diagnostics & Imaging Week Staff Writer
Typically, cutting through the swath of protein biomarkers to develop diagnostic tests is extremely difficult, time consuming and generally relatively not worth the effort.
But the results of the Clinical Proteomic Technology Assessment for Cancer study, which is sponsored by the National Cancer Institute, part of the National Institutes of Health (Bethesda, Maryland) and partner organizations, and appears online in the June 28, 2009 issue of Nature Biotechnology is adding hope toward increasing development of cancer detection methods.
A team of NCI researchers has demonstrated that a new method for detecting and quantifying protein biomarkers in body fluids may ultimately make it possible to screen multiple biomarkers in hundreds of patient samples, thus ensuring that only the strongest biomarker candidates will advance down the development pipeline.
They have developed a method with the potential to increase accuracy in detecting real cancer biomarkers that is highly reproducible across laboratories and a variety of instruments so that cancer can be caught in its earliest stages.
"This targeted analysis will allow you to test different biomarker candidates. Before this it wasn't realistically possible to configure a method that would measure (biomarkers) because they were so numerous," Daniel Liebler PhD, a professor of biochemistry at Vanderbilt University (Nashville, Tennessee) and an author on the study, told Diagnostics & Imaging Week.
Prior to the study, the discovery process typically identified hundreds of candidate biomarkers in each study using small numbers of samples, leading to a very high rate of invalid biomarkers, according to Liebler. The biomarkers that are actually valid that is, true biomarkers must be culled from lengthy lists of candidates, a time-consuming and not always accurate process.
According to the CPTAC center network study, new applications of existing proteomic techniques show promise of greater accuracy. The findings suggest that two technologies multiple reaction monitoring (MRM) coupled with stable isotope dilution mass spectrometry (SID-MS), which is a technique used by protein scientists to measure the abundance of a particular protein in a sample may be suitable for use in preclinical studies to rapidly screen large numbers of candidate protein biomarkers in the hundreds of patient samples necessary for verification.
MRM provides a rapid way to determine whether a candidate biomarker is detectable in blood. This is critically important for clinical use, as well as in being able to assess whether changes in a candidate biomarker correspond with the presence or stage of a disease. A sophisticated type of mass spectrometry, MRM is designed for obtaining the maximum sensitivity for quantifying target compounds in patient samples.
"Our work demonstrates that this technology has the potential to transform how candidate protein biomarkers are evaluated. SID-MRM-MS, combined with complementary techniques, could provide the critical filter to assess protein candidate performance without the immediate need for other detection or quantification tests. This would provide the critical missing component for a systematic biomarker pipeline that bridges discovery and clinical validation," said senior author Steven Carr, PhD, director of the Proteomics Platform at the Broad Institute (Cambridge, Massachusetts). "This is an important step forward for the field of proteomics, one that would not have been possible without the collaborative efforts of the CPTAC partners."
In this study, the researchers demonstrated that MRM is highly sensitive and specific, important characteristics that ensure the detection of real disease-specific biomarkers. In addition, using common samples and standardized protocols, they found that MRM is highly reproducible across laboratories and technology platforms.
Clinical Proteomic Technologies for Cancer will make common samples and standardized protocols available through its reagents data portal, which can be accessed at http://proteomics.cancer.gov.
The study emerged from a memorandum of understanding between the NCI (through Clinical Proteomic Technologies for Cancer) and the FDA to accelerate proteomics technology development and application in clinical settings.