Protein biomarkers have many uses in clinical medicine, but overlooking racial differences in these biomarkers could significantly reduce the quality of medical care given to ethnic minorities.
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Biomarkers are measurable indicators of biological processes. This includes normal biological processes, pathogenic processes, or responses to drug treatments. Biomarkers are extremely useful in clinical medicine, as they are easier to detect and measure than the complex biological events they indicate.
Proteins are particularly useful as biomarkers, as they are often the effectors of disease and the targets of therapeutic treatments. Protein biomarkers can aid in disease diagnosis, inform prognosis, and may be used to monitor the responses of individual patients to drug treatments.
Why are Protein Biomarkers Useful?
Protein biomarkers can improve patient outcomes by facilitating early disease diagnosis and identifying patients that could benefit from specific therapies. For example, in certain types of breast cancer, human epidermal growth factor receptor 2 (HER2) is overexpressed. In such cases, HER2 is a valuable marker for identifying cancer patients who may benefit from HER2-targeted therapies.
Biomarkers are useful in monitoring a drug treatment's efficacy during clinical trials. Efficacy biomarkers can indicate whether individual patients are responding to a drug, meaning companies are able to stop clinical trials earlier if treatment is not working, saving time and resources.
Protein biomarkers also improve the safety of clinical trials as they help define appropriate drug dosages and can be used to identify patients more susceptible to a drug's adverse effects. Biomarkers often detect evidence of drug-induced kidney injury during clinical trials, which allows drugs to be reformulated or discarded before further damage is done.
Improvements in the safety of disease diagnosis are also made possible by observing biomarkers. For instance, scientists can test for the presence of protein biomarkers in the ocular fluid of patients with uveal melanoma, a form of eye cancer. This is a safer method of predicting metastatic risk than conducting biopsies of eye tissue.
There are many benefits to the use of biomarkers in clinical medicine. However, race-associated differences in certain protein biomarkers could reduce the performance of biomarker analyses and potentially result in poorer health outcomes for ethnic minorities.
Race-associated Differences in Protein Biomarkers
Significant racial differences have been detected in the protein biomarkers used to diagnose Alzheimer's. One of the hallmark features of Alzheimer's disease is the toxic build-up of two proteins: tau and amyloid-β. Therefore, the concentration of these proteins can be measured to detect people with early-stage Alzheimer's so that treatment plans can be devised.
However, a study conducted by Morris et al. (2019) found significant differences in the concentrations of tau protein in the cerebrospinal fluid of African American individuals compared with white individuals.
Across the 1255 adults studied, average tau concentrations for white people were 443 pg/mL, whereas they were 294 pg/mL for African Americans. This difference was even more pronounced in individuals that carried the Alzheimer's risk gene APOEε4, suggesting that the interaction between APOEε4 and tau could differ between the two races.
Although this study only involved participants of two different ethnicities, the findings could still have significant implications for diagnosing and treating Alzheimer's disease in people of different races.
Protein biomarkers indicative of other diseases have also been shown to differ with race. For example, differences in the association between inflammatory biomarkers and chronic kidney disease have been detected across ethnic groups.
Race-specific differences are also present in the biomarkers capable of detecting active lupus nephritis, a complication of the autoimmune disease lupus that causes the kidneys to become inflamed.
Furthermore, in a study by Tahmasebi et al. (2020), the concentrations of 7 commonly used biomarkers were found to differ significantly between children of different ethnicities. These biomarkers included follicle-stimulating hormone (FSH), ferritin, and immunoglobulin.
Why is biomarker testing so important for certain ethnic groups, such as African Americans?
What are the Consequences of these Differences?
Protein biomarkers are extremely valuable tools that have many applications in clinical medicine. However, much of what we know about protein biomarkers is based on research conducted on predominantly white individuals.
If protein biomarkers that exhibit racial differences are used to inform diagnoses and treatments, inequalities in disease management across different ethnic groups could be exacerbated. As such, it is imperative that groups of participants used in future medical research accurately reflect the full diversity of the general population.
Additionally, further research must be done to identify the underlying reasons behind the racial differences observed and to investigate the possibility of racial differences in other protein biomarkers.
This would help to ensure all patients receive the best possible care by facilitating the identification of biomarkers that perform equally well in all ethnic groups or, alternatively, allowing the underlying reasons behind racial differences in protein biomarkers to be corrected for.
Continue Reading: GC-MS for Biomarker Discovery
Sources:
- Morris, J.C., Schindler, S.E., McCue, L.M., Moulder, K.L., Benzinger, T.L., Cruchaga, C., Fagan, A.M., Grant, E., Gordon, B.A., Holtzman, D.M. and Xiong, C. (2019). Assessment of racial disparities in biomarkers for Alzheimer disease. JAMA Neurology, 76(3), pp.264-273. https://doi.org/10.1001/jamaneurol.2018.4249
- Boschetti, E., D'Amato, A., Candiano, G. and Righetti, P.G. (2018). Protein biomarkers for early detection of diseases: the decisive contribution of combinatorial peptide ligand libraries. Journal of Proteomics, 188, pp.1-14. https://doi.org/10.1016/j.jprot.2017.08.009
- Stanley, S., Vanarsa, K., Soliman, S., Habazi, D., Pedroza, C., Gidley, G., Zhang, T., Mohan, S., Der, E., Suryawanshi, H. and Tuschl, T. (2020). Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities. Nature Communications, 11(1), pp.1-13. https://doi.org/10.1038/s41467-020-15986-3
- Tahmasebi, H., Asgari, S., Hall, A., Higgins, V., Chowdhury, A., Thompson, R., Bohn, M.K., Macri, J. and Adeli, K. (2020). Influence of ethnicity on biochemical markers of health and disease in the CALIPER cohort of healthy children and adolescents. Clinical Chemistry and Laboratory Medicine, 58(4), pp.605-617. https://doi.org/10.1515/cclm-2019-0876
- Griffin, B.R., Faubel, S. and Edelstein, C.L. (2019). Biomarkers of drug-induced kidney toxicity. Therapeutic Drug Monitoring, 41(2), p.213. https://doi.org/10.1097/FTD.0000000000000589
- Mosterd, C.M., Hayfron-Benjamin, C.F., Van Den Born, B.J.H., Maitland-Van der Zee, A.H., Agyemang, C. and Van Raalte, D.H. (2022). Ethnic disparities in the association between low-grade inflammation biomarkers and chronic kidney disease: The HELIUS Cohort Study. Journal of Diabetes and its Complications, 36(8), p.108238. https://doi.org/10.1016/j.jdiacomp.2022.108238
- Mosley, K., Tam, F.W.K., Edwards, R.J., Crozier, J., Pusey, C.D. and Lightstone, L. (2006). Urinary proteomic profiles distinguish between active and inactive lupus nephritis. Rheumatology, 45(12), pp.1497-1504. https://doi.org/10.1093/rheumatology/kel351
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