The cornerstones of medicine are to prevent, diagnose, prognose and treat disease. An essential tool in both clinical and research settings of medicine are biological markers, also referred to as “biomarkers”. According to the National Institutes of Health Biomarkers Definitions Working Group, a biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”1 Biomarkers can therefore be changes in many different characteristics, e.g. blood pressure, metabolites, nucleic acids, and proteins, to name a few.2
The roles of biomarkers in clinical settings are many. Biomarkers can improve the time, cost, and efficacy of diagnosis of disease. Biosensors detecting the biomarkers are often more efficient in diagnosis than relying on the patient’s own perceptions and observable symptoms.
The most common uses of biomarkers are for prognostic and predictive purposes.3 Prognostic biomarkers help clinicians to determine the likely outcome of a medical condition. An example of this is the relation between mutations in the two tumor suppressor genes BRCA1 and BRCA2 and hereditary breast and ovarian cancer. Inheriting mutations of BRCA1 or BRCA2 causes these individuals to have up to 84 % lifetime risk of breast cancer and up to 45 % risk of ovarian cancer.4 Genetic testing is therefore available if inherited BRCA1/2 are suspected within a family and special measures can be taken. These measures vary from regular testing for either cancer type to contralateral mastectomy and prophylactic salpingo-oophorectomy.5
Predictive biomarkers on the other hand, give insight into whether treatment with a given drug will result in effective treatment or not. The response to a given treatment is highly variable, with some individuals showing no effect at a certain dose while the same dose can be lethal for someone else.6 Pharmacogenetic biomarkers can be used to predict drug response of various treatments. Carbamazepine, a drug often used for treating epilepsy, is associated with serious cutaneous adverse reactions in up to 10 % of patients. The hypersensitivity to Carbamazepine is a result of a genetic variation in the human leukocyte antigen (HLA) gene. Individuals with Asian descent have a higher frequency of a genotype causing a 100-fold increase in the risk of an adverse drug response. As a result, it is recommended that genotyping should be performed before Carbamazepine is administered.7
A potential biomarker which has garnered a lot of attention lately is interleukin 6 (IL6). IL6 is a pro-inflammatory cytokine released from T-lymphocytes during the acute phase of sepsis. IL6 has been proposed as a diagnostic biomarker or a diagnostic aid for early diagnosis of sepsis.8,9 The mortality rate of sepsis is estimated to be close to 22 % globally by the World Health Organization10. The high mortality rate is in part due to the slow diagnostics of sepsis currently in use, which mainly uses multi-step analysis of blood cultures.11 The need for fast detection and diagnosis of sepsis is therefore paramount. Finding biomarkers for sepsis is therefore a promising way forward for better treatments of sepsis.
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3. Brody T. 2016. Chapter 19 – Biomarkers. I: Brody T (red.). Clinical Trials (Second Edition), s. 377–419. Academic Press, Boston.
4. Streff H, Profato J, Ye Y, Nebgen D, Peterson SK, Singletary C, Arun BK, Litton JK. 2016. Cancer Incidence in First- and Second-Degree Relatives of BRCA1 and BRCA2 Mutation Carriers. The Oncologist 21: 869–874.
5. Lee A, Moon B-I, Kim TH. 2020. BRCA1/BRCA2 Pathogenic Variant Breast Cancer: Treatment and Prevention Strategies. Annals of Laboratory Medicine 40: 114–121.
6. Bank PC, Swen JJ, Guchelaar H-J. 2014. Pharmacogenetic biomarkers for predicting drug response. Expert Review of Molecular Diagnostics 14: 723–735.
7. Yip VL, Marson AG, Jorgensen AL, Pirmohamed M, Alfirevic A. 2012. HLA Genotype and Carbamazepine-Induced Cutaneous Adverse Drug Reactions: A Systematic Review. Clinical Pharmacology & Therapeutics 92: 757–765.
8. Ma L, Zhang H, Yin Y, Guo W, Ma Y, Wang Y, Shu C, Dong L. 2016. Role of interleukin-6 to differentiate sepsis from non-infectious systemic inflammatory response syndrome. Cytokine 88: 126–135.
9. Spittler A, Razenberger M, Kupper H, Kaul M, Hackl W, Boltz-Nitulescu G, Függer R, Roth E. 2000. Relationship Between Interleukin-6 Plasma Concentration in Patients with Sepsis, Monocyte Phenotype, Monocyte Phagocytic Properties, and Cytokine Production. Clinical Infectious Diseases 31: 1338–1342.
10. Sepsis. WWW-document: https://www.who.int/news-room/fact-sheets/detail/sepsis. Retrieved 2022-03-27.
11. Kumar S, Tripathy S, Jyoti A, Singh SG. 2019. Recent advances in biosensors for diagnosis and detection of sepsis: A comprehensive review. Biosensors and Bioelectronics 124–125: 205–215.