In a sense, clinical laboratory professionals have always been in the biomarker business: they seek signs of diseases or disorders, or measures of organ function or health status (such as cholesterol) in blood, urine, tissue, or other biological samples. Yet the term itself gained widespread currency only in the 1980s. In 1998, the National Institutes of Health (NIH) Biomarkers Definitions Working Group defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” With that, biomarkers started to be understood as either prognostic or predictive, and research as the quest to find increasingly useful ones gained new energy and impetus. A wide range of conditions have yielded biomarkers to determined researchers, some of whom are seeking to find novel biomarkers that are more predictive than established ones.
For example, novel biomarkers are increasing the power to predict therapeutic response in lupus. Approximately half of all patients with lupus develop LN, an immune complex-mediated glomerulonephritis. Scientists at the Medical University of South Carolina found that “traditional” biomarkers—protein-to-creatinine ratios, and markers of standard kidney function—did not predict response as well as a panel of urinary biomarkers reflecting inflammatory cell activation (cytokines), signals for homing to the kidney (chemokines), activation of inflammatory cells (growth factors), and cellular damage.
Biomarkers may help better predict who will have a stroke. Researchers from the Boston University Schools of Medicine and Public Health measured the levels of 15 biomarkers associated with inflammation in the blood of people who had never had a stroke. They discovered that four were associated with an increased risk. People with elevated homocysteine were 32 percent more likely to have a stroke during the study period. Those with high vascular endothelial growth factor were 25 percent more likely. Those with high ln-C reactive protein were 28 percent more likely, and those with high ln-tumor necrosis factor receptor 2 were 33 percent more likely to have a stroke. When combined with other known risk factors, this may prove to be crucial clinical information.
An imaging study recently conducted by scientists at several institutions suggests a link between inflammatory biomarkers and increased heart disease in men with HIV. After researchers used CT scanning to identify early signs of coronary artery disease in study participants, they were also measured for the presence of seven inflammatory biomarkers. Men infected with HIV had higher levels of the biomarkers than those who were not infected. That may explain in part why people infected with HIV have a higher risk of heart disease.
(It is interesting that inflammatory biomarkers figure in all three of the above studies. The idea that cytokines and inflammation may play a more far-reaching role in disease than medical science has realized is itself gaining increasing currency, in part due to studies like these.)
One more interesting study to report before I run out of column: the longstanding effort to find better ways to predict the virulence of prostate cancer—in order to better treat, or choose not to treat, patients—may be getting an assist from biomarker research. Scientists at the Princess Margaret Cancer Centre in Toronto have discovered biomarkers using non-invasive liquid biopsies to identify aggressive disease before surgery. Using targeted proteomics, they quantified hundreds of proteins in urine samples to identify liquid biopsy signatures. Then they used data from mass spectrometry to identify the biomarkers for aggressive prostate cancer.
Will these biomarkers, and others that have recently been reported, one day be the basis of commercial assays that you will routinely run? Certainly, some of them will.
