Tue Mar 16 2021

Biomarkers serve as biological characteristics that clinicians can measure to indicate normal or pathological processes, or responses to interventions. In clinical practice, they are essential for the early diagnosis and effective management of diseases, offering a prompt, non-invasive, and cost-effective diagnostic method. Beyond diagnosis, healthcare professionals use biomarkers to monitor treatment progress, assess disease recurrence risk, and evaluate prognosis.

Clinical Biomarkers

Clinical biomarkers can be categorized into the following groups depending on their usage in clinical practice1:

  • Diagnostic biomarkers help detect or confirm a disease’s presence and identify sub-types of a disease.
  • Monitoring biomarkers are measurable over time to check disease status or the impact of treatments.
  • Pharmacodynamic/Response biomarkers change in response to therapy or environmental exposure, guiding treatment decisions.
  • Predictive biomarkers forecast treatment benefits or the likelihood of treatment success in certain patient groups.
  • Prognostic biomarkers predict disease recurrence, progression, or clinical events in diagnosed patients.
  • Safety biomarkers indicate toxicity risks or adverse reactions to interventions or exposures.
  • Susceptibility/Risk biomarkers assess disease development risk in healthy individuals.

Among the most common general biomarkers are CRP and suPAR:

  • C-reactive Protein (CRP): An inflammatory protein, CRP levels spike in the blood during inflammation, such as in rheumatoid arthritis, certain cardiovascular diseases, and infections. Levels can soar from about 1 µg/mL to over 500 µg/mL within 24-72 hours in severe conditions, decreasing rapidly as inflammation subsides.
  • Soluble urokinase plasminogen activator receptor (suPAR): The soluble form of the uPAR protein found on immune cells, suPAR levels in the blood increase with inflammation severity. It serves as a marker for monitoring disease progression and treatment effects. While healthy individuals typically have suPAR levels ranging from 1-3 ng/ml, these can exceed 10 ng/ml in critical conditions.

Biomarkers to Detect Different Diseases

The important biomarkers currently used in clinical practice for screening and diagnosis of different diseases are listed as follows5,6,7,8,9,10,11,12 :

Biomarkers for brain injury

  • Glial fibrillary acidic protein
  • S100B
  • UCHL-1

Biomarkers for heart failure

  • B-type natriuretic peptide (BNP)
  • Galectin-3
  • Neutrophil gelatinase-associated lipocalin (NGAL)
  • Mid-regional pro-adrenomedullin (MR-ProADM)

Biomarkers for stress

  • Cortisol
  • Adrenaline
  • Noradrenaline
  • DHEA

Biomarkers for sepsis (LINK)

  • C-reactive Protein
  • Procalcitonin

Inflammatory biomarkers (LINK)

  • Cytokines
  • C-reactive Protein
  • Serum Amyloid A
  • COX-2 Expression

Biomarkers for Alzheimer’s

  • Amyloid beta
  • Tau protein
  • Phosphorylated tau

Biomarkers for Cancer (LINK)

  • Prostate-specific antigen (PSA)
  • Carcinoembryonic antigen (CEA)
  • HER2
  • Alfa-fetoprotein

Biomarkers for Cardiac Disease (LINK)

  • B-type natriuretic peptide (BNP)
  • Troponin
  • C-reactive Protein
  • Myeloperoxidase (MPO)
  • Fibrinogen

Biomarkers in neurodegenerative diseases

  • Tau
  • Phosphorylated tau
  • Amyloid beta

Biomarkers of liver function (LINK)

  • Alanine amino transferase (ALT)
  • Aspartate amino transferase (AST)
  • Alkaline Phosphatase (ALP)
  • Serum Bilirubin

Biomarkers for acute kidney injury (LINK)

  • Neutrophil gelatinase-associated lipocalin (NGAL)
  • Kidney injury molecule-1 (KIM 1)
  • Cystatin C
  • IL-18

Biomarkers in Other Areas

Biomarkers measured for other health issues are as follows13,14,15 :

Biomarkers for ageing (LINK)

  • DNA repair
  • Telomeres
  • Epigenetic modifications
  • Cell senescence

Biomarkers for wound healing (LINK)

  • Tissue biomarkers- c-myc and B-catenin
  • Metalloproteinase enzymes (wound fluid biomarkers)
  • CD 34+/CD45-

Biomarkers in medicine (LINK)

  • Cholesterol
  • Triglycerides
  • HDL-cholesterol
  • LDL-cholesterol
  • C-Peptide

suPAR as a Biomarker: How to use it across diseases

The biomarker suPAR is the soluble form of the cell membrane-bound protein uPAR, which is expressed mainly on leucocytes (white blood cells) including neutrophils, lymphocytes, monocytes, and macrophages. Leucocytes form an integral part of the body’s immune system and are involved in the body’s inflammatory response to diseases and injuries. All human beings have a baseline level of suPAR, which is low but increases with age. suPAR levels in the body are elevated in the presence of diseases16,17.

Scientific studies have shown that suPAR is associated with a number of chronic diseases (including cardiovascular, hepatic, renal, and pulmonary diseases). Moreover, suPAR level is a predictor of a negative outcome (NPV) of various infectious diseases (tuberculosis, HIV, malaria, sepsis, meningitis, pneumonia). suPAR can be used as a prognostic as well as a predictive biomarker of various conditions. The concentration of suPAR in the bloodstream can also be monitored to assess the progression of a disease and evaluate efficacy of a treatment plan18,19,20,21.

Kinetics of suPAR

In normal conditions, the suPAR blood level is stable with no diurnal variation or changes following fasting. suPAR can be measured in blood, plasma, urine, cerebrospinal fluid, ascites fluid and pleural fluid22. The level of suPAR increases and decreases with progression and improvement of a disease, respectively, but more slowly compared to e.g. C-reactive protein (CRP).

Plasma suPAR is a robust biomarker which undergoes minimal changes during laboratory handling and storage. Plasma suPAR level remains stable for at least 24 hours at room temperature and for at least five repeated freeze/thaw cycles23.

suPAR in Clinical Practice

In the first week of febrile neutropenia, serum suPAR levels have been found to have a sensitivity of 100%, a specificity of 69%, a negative predictive value (NPV) of 100%, and a positive predictive value (PPV) of 70%.Currently, no alternative to suPAR with the same strong NPV have been found. High NPV and PPV (87% and 91%, respectively with a cut of value of 2.8ng/mL) have also been found when testing the prognosis of patients with systemic inflammatory response syndrome (SIRS) patients.34 In children with SIRS, a NPV and PPV, both of 96% for suPAR have been reported24,25.

Studies have shown that increased levels of suPAR can predict disease outcome in various forms of cancer and infectious diseases. In chronic liver disease, with progressive liver fibrosis, the suPAR level is increased and correlates with poor prognosis. Also, cirrhotic patients have higher suPAR levels than non-cirrhotic patients. Circulating suPAR levels closely correlate with liver function, fibrosis markers, systemic inflammation and renal function26,27.

1. Califf RM. Biomarker definitions and their applications. Exp Biol Med (Maywood). 2018;243(3):213–221. doi:10.1177/1535370217750088.
2. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018;9: 754. Published 2018 Apr 13. doi:10.3389/fimmu.2018.00754.
3. da Silva et.al. Evaluation of the diagnostic potential of uPAR as a biomarker in renal biopsies of patients with FSGS. Disease Markers. 2019.
4. The diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) compared to C-reactive protein (CRP) and procalcitonin (PCT) in children with systemic inflammatory response syndrome (SIRS), Melis Şirinoğlu et al, 2016, Journal of Infection and Chemotherapy 23
5. Sharma N, Singh AN. Exploring Biomarkers for Alzheimer’s Disease. J Clin Diagn Res. 2016;10(7):KE01–KE6. doi:10.7860/JCDR/2016/18828.8166
6. Hala et.al. Cancer Biomarkers: Role of Biomarkers in Medicine, Mu Wang and Frank A. Witzmann. IntechOpen Books. 2016. https://www.intechopen.com/books/role-of-biomarkers-in-medicine/cancer-biomarkers
7. Huang et.al. Biomarkers of cardiovascular disease. Disease Markers. 2017.
8. Gowda S, Desai PB, Kulkarni S. A review on laboratory liver function tests. The Pan African Medical Journal. 2009; 3: 17.
9. Alge JL, Arthur JM. Biomarkers of AKI: A review of mechanistic relevance and potential therapeutic implications. Clinical Journal of American Society of Nephrology. 2015. 10(1).
10. Dadas A, Washington J, Diaz-Arrastia R, Janigro D. Biomarkers in traumatic brain injury (TBI): a review. Neuropsychiatr Dis Treat. 2018;14: 2989–3000. Published 2018 Nov 8. doi:10.2147/NDT.S125620
11. Nelson GE, Mave V, Gupta A. Biomarkers for sepsis: A review with special attention to India. Blood Stream Infections. 2014.
12. Brenner et.al. A review of the application of inflammatory biomarkers in epidemiologic cancer research. Cancer Epidemiology, Biomarkers & Prevention. 2014. 23(9).
13. Xia X, Chen W, McDermott J, Han JJ. Molecular and phenotypic biomarkers of aging. F1000Res. 2017;6: 860. Published 2017 Jun 9. doi:10.12688/f1000research.10692.1
14. Lindley et.al. Biology and biomarkers for wound healing. Plastic and Reconstructive Surgery. 2017. 138(3).
15. Mayeux R. Biomarkers: Potential Uses and Limitations. NeuroRx. 2004 Apr; 1(2): 182–188.
16. Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 2002; 3: 932–43.
17. Smith HW, Marshall CJ. Regulation of cell signalling by uPAR. Nat Rev Mol Cell Biol 2010; 11: 23–36.
18. Eugen-Olsen, J. et al. Circulating soluble urokinase plasminogen activator receptorpredicts cancer, cardiovascular disease, diabetes and mortality in the generalpopulation. J. Intern. Med. 2010;268, 296–308.
19. Reichsoellner M, Raggam RB, Wagner J, Krause R, Hoenigl M. Clinical evaluation of multiple inflammation biomarkers for diagnosis and prognosis for patients with systemic inflammatory response syndrome. Journal of clinical microbiology 2014;52:4063-6.
20. Gumus A, Altintas N, Cinarka H, et al. Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD. International journal of chronic obstructive pulmonary disease 2015;10:357-65.
21. Persson M, Ostling G, Smith G, et al. Soluble urokinase plasminogen activator receptor: a risk factor for carotid plaque, stroke, and coronary artery disease. Stroke; a journal of cerebral circulation 2014;45: 18-23.
22. Thunø M, Macho B, Eugen-Olsen J. suPAR: The molecular crystal ball. Dis Markers. 2009;27(3):157-72. 2. Eugen-Olsen, J. et al. Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J. Intern. Med. 2010;268, 296–308.
23. Development and Validation of a Multiplex Add-On Assay for Sepsis Biomarkers Using xMAP Technology Kristian Kofoed,1,2* Uffe Vest Schneider,1 Troels Scheel,1 Ove Andersen,1,2 and Jesper Eugen-Olsen1, Clinical Chemistry 52:7 1284–1293 (2006)
24. Rasmussen LJ, et al. Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort study. Emerg Med J.2016 33(11):769-775.
25. The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in systemic inflammatory response syndrome, Yilmaz et al, clinical Biochemistry, 2011;44(14-15):1227-1230
26. Feldman. Sleisenger and Fordtran’s gastrointestinal and liver disease. 9th ed. Philadelphia, PA, United States: Saunders: an imprint of Elsevier, 2010.
27. Circulating soluble urokinase plasminogen activator is elevated in patients with chronic liver disease, discriminates stage and aetiology of cirrhosis and predicts prognosis, Henning W. Zimmermann, Alexander Koch, Sebastian Seidler, Christian Trautwein and Frank Tacke, Liver International ISSN 1478-3223


published suPAR studies in leading medical journals

Nature Medicine Logo
Science Journal Logo
JAMA Pediatrics Logo

The suPARnostic® brand consists of four products:

Quick Triage

Quick Triage

A Point of Care Solution


For Automated Systems


Clinical and Research


Point-of-care finger prick

New Webinar


Catch COVID-19

-Improve your triage

Sign up to view webinar recording

View recording

suPARnostic® by ViroGates