The fascinating world of biomarkers
Biomarkers: millions of diagnostic possibilities
My greatest interests include research on biomarkers – naturally occurring indicators enabling the diagnosis of a disease or the assessment of the risk of complications in patients with an already diagnosed disease. In particular, I am fascinated by scientific works on cardiovascular diseases.
Thousands of scientists from around the world conduct research on biomarkers such as microRNA, extracellular vesicles, cytokines and other proteins. The aim of these studies is most often to assess usefulness of a given particle in diagnosis, predicting severity of the course [of a disease] or foreseeing the patient’s response to treatment.
There are a lot of these potential biomarkers: over 2,500 microRNAs alone. Multiplying this by the number of all disease entities will give us a huge number. If a single study were to evaluate just one particle in one disease, millions of studies would be necessary just to evaluate the value of these biomarkers. Yet, there are many more research problems.
Therefore, during one study, many different biomarkers are often first assessed in a more qualitative way, using techniques such as microarrays. Then, quantitative measurements are made of those particles that have shown potential diagnostic usefulness at an earlier stage.
Biomarkers in diagnosing diseases
Although the diagnostic criteria for most diseases are clearly defined, there are still many diseases in which they remain ambiguous. At the same time, to diagnose many diseases it is necessary to perform invasive procedures, potentially associated with a risk of complications. Another problem is availability of highly specialized imaging tests, often necessary to make a diagnosis. Biomarkers, ultimately available in everyday clinical practice, may be the solution to these problems.
The key to success is to identify those particles for which the assessment of their concentration in blood, saliva, urine or other easily accessible material will allow for the diagnosis of the disease while maintaining sensitivity and specificity at an least the same level as that of reference method (e.g. imaging).
One of the most frequently used diagnostic biomarkers are cardiac troponins measured to diagnose recent myocardial infarction. Although cardiac troponins have very high sensitivity, they have low specificity, which means that their blood concentration is increased in many other cardiac diseases apart from myocardial infarction, as well as in non-cardiac diseases such as cerebral apoplexy or chronic kidney disease. Therefore, scientists are looking for alternative possibilities for early identification of patients with infarction, which would enable the diagnosis to be made faster, perhaps even before cardiomyocyte necrosis occurs.
In addition to diagnosing the disease, it is also very important to determine its stage. This is also important for logistical reasons. With limited medical staff resources, it seems crucial to direct actions first to those patients who require help most urgently. Also in this regard, many studies have shown that biomarkers enable such an assessment of the severity of the disease.
Biomarkers and patient prognosis
The second extremely important issue is the patient prognosis. It is important both for the medical team and, above all, for the patient. Forecasting is nothing more than estimating the probability of what can happen to a given patient based on available clinical data – thousands or even millions of previous patients with a similar condition, with known characteristics and final results. However, biological differences make each patient unique. Although, with a sufficiently large number of tests, the prognosis can be quite precise, when asked by a patient: “Doctor, what will happen to me next?”, it is not possible to give a clear answer and all that remains is to provide percentages that may turn out to be inaccurate.
Supplementing diagnostic algorithms with biomarkers has a potential to increase the precision of responses and improve the accuracy of prognosis, thus revolutionizing the risk assessment for individual patients.
The patient’s response to the therapy
Another important function that biomarkers perform is the prediction of a patient’s response to therapy. There are many clinical cases in which medical consultants make decisions regarding the method of treatment. Very often it happens that the situation is not black-and-white and making a choice is therefore very difficult. Each additional factor that would indicate the advantage of one of the methods would significantly facilitate making the right decision. Therefore, biomarkers are being sought that enable the division of patients into those who will respond well to a given therapy (good responders) and those who will respond poorly or not at all (poor responders, non-responders). It is crucial to classify the patient into one of these groups before proceeding with the therapy. This has an extremely important impact on optimizing the ratio of expected benefits to assumed losses.
Biomarker research often leads to the discovery of new therapeutic agents. Observing differences in the concentration of a given particle between sick and healthy people leads to the question whether this correlation has a cause-and-effect relationship. In other words, is this changed level only a marker of a disease, or perhaps it causes its occurrence. If data point to the latter scenario, this opens up treatment options by trying to lower or increase the levels of that molecule, for example a protein, nucleic acid or their derivatives.
The role of biomarkers in personalized medicine
All these problems follow the trend of personalized medicine – “tailored” to the needs of each patient. Based on many hitherto studies, it is possible to identify those particles that are useful in assessing specific disease entities. Having such a panel of biomarkers, it is possible to obtain a specific “molecular fingerprint” of the patient, which contains information about whether we can recognize a given disease in them, what their prognosis is, and, above all, what treatment is best to use – what will bring the most benefits and what therapy is associated with a disproportionately high risk.
Of course, we also obtain answers to these questions based on a clinical examination and additional tests – imaging and laboratory tests. However, the dynamic development of biomarkers means that our perception of reality is becoming more and more precise and allows us to “tailor” therapies to the patient’s needs even more precisely.
About research conducted at the 1st Department and Clinic of Cardiology of the Medical University of Warsaw
In my research I always start with a thorough literature review. As part of my activities in the 1st Department and Clinic of Cardiology of the Medical University of Warsaw, headed by Prof. Marcin Grabowski (previously by Prof. Grzegorz Opolski), I summarized the available literature on the importance of biomarkers in a series of publications: microRNAs in myocarditis and in the monitoring of antiplatelet therapy and extracellular vesicles in atrial fibrillation. At the same time, under the supervision from my supervisor and mentor, habilitated doctor Aleksandra Gąsecka, I started my own research on the use of biomarkers in patients with aortic stenosis for the purpose of assessing the response to treatment using transcatheter aortic valve implantation.
The subject of biomarkers is undoubtedly fascinating, but still full of many puzzles and unknowns, and therefore extremely attractive to scientists. Many things remain to be discovered. The most important thing, however, should always be not to forget what is at the heart of all this research: patient care. The desire to discover reality and know the truth motivated by the desire to help another person is something truly beautiful. I believe that science is heading in this direction.
Grzegorz Procyk is the winner of the 1st degree award of the Rector of the Medical University of Warsaw for a series of works on markers in cardiovascular diseases, the winner of the scholarship of the Minister of Health for significant scientific achievements and the winner of the 2nd edition of the “Talents of Tomorrow” grant program in which he received a grant for the implementation of the project titled “Interleukin-6 and the role of lipoprotein(a) in the pathophysiology of aortic stenosis”.
Ed. and photo.: Communication and Promotion Office