Unfortunately, only 50 percent of breast cancers are localized at the time of diagnosis, in part, due to the quality of the tools used to screen for breast cancer. For example, the effectiveness of mammography is still being debated, while serum-based tumor markers still lack adequate sensitivity and specificity for detecting early stage carcinoma.
Identification of disease-associated proteins could be a solution for early detection of breast cancers. However, scientists have found that some technologies for protein identification are too labor intensive and are not effective as a diagnostic tool (polyacrylamide gel electrophoresis), while others experience signal background problems which precluded their use as a high-throughput screening tool for protein analysis (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry).
A team of researchers have now set out to examine whether surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI) may be a practical and effective method for identifying potential biomarkers of early stage breast cancer. The authors of “Identification of Serum Biomarkers to Detect Breast Cancer Using Proteomics and Bioinformatics Approaches,” are Jinong Li, Zhen Zhang, Jason Rosenzweig, Young Y. Wang, and Daniel W. Chan, all from the Department of Pathology at Johns Hopkins Medical Institutions in Baltimore, Md.
The researchers’ study appears in the August edition of Clinical Chemistry, the scientific journal of the American Association for Clinical Chemistry (AACC). Publication was timed to coincide with the organization’s 54th Annual Meeting, which is being held at the Orange County Convention Center, Orlando, Fla., July 28-August 1, 2002. More than 11,000 attendees are expected for the meeting. AACC (http://www.aacc.org/) is the scientific organization for clinical laboratory professionals, physicians, and research scientists. Their primary commitment is the understanding of laboratory testing to identify, monitor and treat human disease.
Background
SELDI is a chip-based molecular imaging process that can be compared to the imaging process that develops photographic film. The small biochips at the heart of SELDI are similar to the silicon wafers used to make computer chips, but their surface is coated with an active layer of molecular "bait" designed to capture biomolecules such as DNA or proteins. These chips are then exposed to the biomaterial to be imaged, which is contained in a matrix of a patient's blood or urine. After exposure, the molecular image captured on the chip's active surface is developed in a manner that maximizes the visibility of those molecules captured. The biochips are then "read" with rapid pulses of laser energy to generate a digital image of the molecule captured on the surface of the biochips. SELDI proponents claim that this process offers the earliest possible detection of disease onset; the ability to accurately assess disease type and level of disease progression; and the ability to routinely monitor how an individual patient is responding to a chosen therapy.
Methodology
The Hopkins researchers obtained 169 serum samples from the institution’s serum banks. The cancer group consisted of 103 serum samples from breast cancer patients at different clinical stages, 41 control samples from women who were free of cancer, and 25 women with benign breast disease. Diluted serum samples were applied to immobilized metal affinity capture Ciphengen ProteinChip®. Complex proteins from different diagnostic groups were then profiled and analyzed.
Results
The researchers selected three biomarkers based on their collective contribution to the statistically significant separation between stages 0-I breast cancer patients and non-cancer controls. This same separation was observed with independent test data of patients with stages II and stage III breast cancer.
A cross validation of the data, derived by multivariate logistic regression, showed a method sensitivity of 93 percent for all cancer patients and a specificity of 91 percent in the control group.
Conclusions
The authors state that the high sensitivity and specificity achieved in this study gives evidence that SELDI mass spectrometry could lead researchers to the discovery of additional biomarkers that would indicate early stage breast carcinoma, and that this technology could fill a gap that now exists in breast cancer prevention.
Editor’s Note: To interview Dr. Chan or a member of the research team, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com.
Or contact the AACC Newsroom at: 407.685.4215.