Biomarker (medicine)
In medicine, a biomarker is a measurable
A biomarker can be a substance that is introduced into an organism as a means to examine organ function or other aspects of health. For example, rubidium chloride is used in isotopic labeling to evaluate perfusion of heart muscle. It can also be a substance whose detection indicates a particular disease state, for example, the presence of an antibody may indicate an infection. More specifically, a biomarker indicates a change in expression or state of a protein that correlates with the risk or progression of a disease, or with the susceptibility of the disease to a given treatment. Biomarkers can be characteristic biological properties or molecules that can be detected and measured in parts of the body like the blood or tissue. They may indicate either normal or diseased processes in the body.[3] Biomarkers can be specific cells, molecules, or genes, gene products, enzymes, or hormones. Complex organ functions or general characteristic changes in biological structures can also serve as biomarkers. Although the term biomarker is relatively new, biomarkers have been used in pre-clinical research and clinical diagnosis for a considerable time.[4] For example, body temperature is a well-known biomarker for fever. Blood pressure is used to determine the risk of stroke. It is also widely known that cholesterol values are a biomarker and risk indicator for coronary and vascular disease, and that C-reactive protein (CRP) is a marker for inflammation.
Biomarkers are useful in a number of ways, including measuring the progress of disease, evaluating the most effective therapeutic regimes for a particular cancer type, and establishing long-term susceptibility to cancer or its recurrence. for cancer.
It is necessary to distinguish between disease-related and drug-related biomarkers. Disease-related biomarkers give an indication of the probable effect of treatment on patient (risk indicator or predictive biomarkers), if a disease already exists (diagnostic biomarker), or how such a disease may develop in an individual case regardless of the type of treatment (prognostic biomarker). Predictive biomarkers help to assess the most likely response to a particular treatment type, while prognostic markers shows the progression of disease with or without treatment.[8] In contrast, drug-related biomarkers indicate whether a drug will be effective in a specific patient and how the patient's body will process it.
In addition to long-known parameters, such as those included and objectively measured in a
The "classic" biomarker in medicine is a laboratory parameter that the doctor can use to help make decisions in making a diagnosis and selecting a course of treatment. For example, the detection of certain autoantibodies in patient blood is a reliable biomarker for autoimmune disease, and the detection of rheumatoid factors has been an important diagnostic marker for rheumatoid arthritis (RA) for over 50 years.[9][10] For the diagnosis of this
There are also more and more indications that ACPAs can be very useful in monitoring the success of treatment for RA.
According to Häupl T. et al. prediction of response to treatment will become the most important aim of biomarker research in medicine. With the growing number of new
An NIH study group committed to the following definition in 1998: "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention." In the past, biomarkers were primarily physiological indicators such as blood pressure or heart rate. More recently, biomarker is becoming a synonym for molecular biomarker, such as elevated prostate specific antigen as a molecular biomarker for prostate cancer, or using enzyme assays as liver function tests. There has recently been heightened interest in the relevance of biomarkers in oncology, including the role of KRAS in colorectal cancer and other EGFR-associated cancers. In patients whose tumors express the mutated KRAS gene, the KRAS protein, which forms part of the EGFR signaling pathway, is always 'turned on'. This overactive EGFR signaling means that signaling continues downstream – even when the upstream signaling is blocked by an EGFR inhibitor, such as cetuximab (Erbitux) – and results in continued cancer cell growth and proliferation. Testing a tumor for its KRAS status (wild-type vs. mutant) helps to identify those patients who will benefit most from treatment with cetuximab.
Currently, effective treatment is available for only a small percentage of cancer patients. In addition, many cancer patients are diagnosed at a stage where the cancer has advanced too far to be treated. Biomarkers have the ability to greatly enhance cancer detection and the drug development process. In addition, biomarkers will enable physicians to develop individualized treatment plans for their cancer patients; thus allowing doctors to tailor drugs specific to their patient's tumor type. By doing so, drug response rate will improve, drug toxicity will be limited and costs associated with testing various therapies and the ensuing treatment for side effects will decrease.[16]
Biomarkers also cover the use of molecular indicators of environmental exposure in epidemiologic studies such as human papilloma virus or certain markers of tobacco exposure such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). To date no biomarkers have been established for head and neck cancer.
Biomarker requirements
For chronic diseases, whose treatment may require patients to take medications for years, accurate diagnosis is particularly important, especially when strong side effects are expected from the treatment. In these cases, biomarkers are becoming more and more important, because they can confirm a difficult diagnosis or even make it possible in the first place.[17] A number of diseases, such as Alzheimer's disease or rheumatoid arthritis, often begin with an early, symptom-free phase. In such symptom-free patients there may be more or less probability of actually developing symptoms. In these cases, biomarkers help to identify high-risk individuals reliably and in a timely manner so that they can either be treated before onset of the disease or as soon as possible thereafter.[18][19]
In order to use a biomarker for diagnostics, the sample material must be as easy to obtain as possible. This may be a blood sample taken by a doctor, a urine or saliva sample, or a drop of blood like those diabetes patients extract from their own fingertips for regular blood-sugar monitoring.
For rapid initiation of treatment, the speed with which a result is obtained from the biomarker test is critical. A rapid test, which delivers a result after only a few minutes, is optimal. This makes it possible for the physician to discuss with the patient how to proceed and if necessary to start treatment immediately after the test.
Naturally, the detection method for a biomarker must be accurate and as easy to carry out as possible. The results from different laboratories may not differ significantly from each other, and the biomarker must naturally have proven its effectiveness for the diagnosis, prognosis, and risk assessment of the affected diseases in independent studies.
A biomarker for clinical use needs good sensitivity and specificity e.g. ≥0.9, and good specificity e.g. ≥0.9[20] although they should be chosen with the population in mind so positive predictive value and negative predictive value are more relevant.
Biomarker classification and application
Biomarkers can be classified based on different criteria.
Based on their characteristics they can be classified as
biomarkers.Biomarkers can also be classified based on their application such as diagnostic biomarkers (i.e., cardiac troponin for the diagnosis of
Classes
Four broad classes of biomarkers are diagnostic biomarkers, prognostic biomarkers, predictive biomarkers and pharmacodynamic biomarkers.
Diagnostic
Prognostic
Prognostic biomarkers give intervention-independent information on disease status and outcome prediction. Prognostic biomarkers can signify individuals in the latent period of a disease's natural history, allowing optimal therapy and prevention until the disease's termination. Prognostic biomarkers give information on disease status by measuring the internal precursors that increase or decrease the likelihood of attaining a disease. For example, blood pressure and cholesterol are biomarkers for CVD.[1] Prognostic biomarkers can be direct or indirect to the causal pathway of a disease. If a prognostic biomarker is a direct step in the causal pathway, it is one of the factors or products of the disease. A prognostic biomarker could be indirectly associated with a disease if it is related to a change caused by the exposure, or related to an unknown factor connected with the exposure or disease.[24]
Predictive
Predictive biomarkers measure the effect of a drug and tell if the drug is having its expected activity, but do not offer any direct information on the disease.
Pharmacodynamic
Types
Biomarkers validated by genetic and molecular biology methods can be classified into three types.[26]
- Type 0 — Natural history markers
- Type 1 — Drug activity markers
- Type 2 — Surrogate markers
Discovery of molecular biomarkers
Molecular biomarkers have been defined as biomarkers that can be discovered using basic and acceptable platforms such as genomics and proteomics. Many genomic and proteomics techniques are available for biomarker discovery and a few techniques that are recently being used can be found on that page. Apart from genomics and proteomics platforms biomarker assay techniques, metabolomics, lipidomics, glycomics, and secretomics are the most commonly used as techniques in identification of biomarkers.
Clinical applications
Biomarkers can be classified on their clinical applications as molecular biomarkers, cellular biomarkers or imaging biomarkers.
Molecular
Four of the main types of molecular biomarkers are genomic biomarkers, transcriptomic biomarkers, proteomic biomarkers and metabolic biomarkers.
Genomic
Genomic biomarkers analyze DNA by identifying irregular sequences in the
Transcriptomic
Transcriptomic biomarkers analyze all RNA molecules, not solely the exome. Transcriptomic biomarkers reveal the molecular identity and concentration of RNA in a specific cell or population. Pattern-based RNA expression analysis provides increased diagnostic and prognostic capability in predicting therapeutic responses for individuals. For example, distinct RNA subtypes in breast cancer patients have different survival rates.[27]
Proteomic
Cellular
Cellular biomarkers allow cells to be isolated, sorted, quantified and characterized by their
Blood-based protein biomarkers
Blood based protein biomarkers are often used as a diagnostic test that usually monitor one or more protein that are indicative of the presence of disease or disorder or the presence of a disease/disorder subphtnotype. Such a Blood based protein biomarker-based test can aoften be used Bas prognosticator of disease outcome. An example is neuronal Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and Glial fibrillary acidic protein (GFAP) can aid in the diagnosis of the presence a cranial lesion among moderate to mild TBI patients that is otherwise only diagnosable with the use of a CT scan of the head.[29]
Imaging biomarkers
Imaging biomarkers allow earlier detection of disease compared to molecular biomarkers, and streamline translational research in the drug discovery marketplace. For example, one could determine the percent of receptors a drug targets, shortening the time and money of research during the new drug development stage. Imaging biomarkers also are non-invasive, which is a clinical advantage over molecular biomarkers. Some of the image-based biomarkers are
Many new biomarkers are being developed that involve imaging technology. Imaging biomarkers have many advantages. They are usually noninvasive, and they produce intuitive, multidimensional results. Yielding both qualitative and quantitative data, they are usually relatively comfortable for patients. When combined with other sources of information, they can be very useful to clinicians seeking to make a diagnosis.
Cardiac imaging is an active area of biomarker research.
Another new imaging biomarker involves
Imaging disease biomarkers by magnetic resonance imaging (MRI)
To achieve molecular imaging of disease biomarkers using MRI, targeted MRI contrast agents with high specificity and high relaxivity (sensitivity) are required. To date, many studies have been devoted to developing targeted-MRI contrast agents to achieve molecular imaging by MRI. Commonly, peptides, antibodies, or small ligands, and small protein domains, such as
Examples
Embryonic
Embryonic biomarkers are very important to fetuses, as each cell's role is decided through the use of biomarkers. Research has been conducted concerning the use of embryonic stem cells (ESCs) in regenerative medicine. This is because certain biomarkers within a cell could be altered (most likely in the tertiary stage of their formation) to change the future role of the cell, thereby creating new ones. One example of an embryonic biomarker is the protein Oct-4.[32]
Autism
ASDs are complex; autism is a medical condition with several etiologies caused due to the interactions between environmental conditions and genetic vulnerability. The challenge in finding out the biomarkers related to ASDs is that they may reflect genetic or neurobiological changes that may be active only to a certain point.[33] ASDs show heterogeneous clinical symptoms and genetic architecture, which have hindered the identification of common genetic susceptibility factors. Still, many researches are being done to find out the main reason behind the genetic incomparability.
Cancer
Traumatic Brain injury
Traumatic brain injury is a major neurological disorder when the brain is injured by traumatic force such as a bluent trauma or blast over-pressure wave. For the disorders of central nervous system, the neuronal cell body-located
List of Biomarkers
In alphabetic order
- Alanine transaminase (ALT)
- Body fat percentage
- Body mass index
- Body temperature
- Blood pressure
- Blood sugar level
- Complete blood count
- Creatinine
- C-reactive protein (inflammation)
- Glial fibrillary acidic protein (GFAP)
- Heart rate
- Hematocrit (HCT)
- Hemoglobin (Hgb)
- Mean corpuscular volume (MCV)
- Red Blood Cell Count (RBC)
- Thyroid-stimulating hormone (TSH)
- Triglyceride
- Troponin (cardiac TN-T, Tn-I)
- Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1)
- Waist circumference
- Waist-to-hip ratio(WHR)
Potential disadvantages
Not all biomarkers should be used as surrogate endpoints to assess clinical outcomes. Biomarkers can be difficult to validate and require different levels of validation depending on their intended use. If a biomarker is to be used to measure the success of a therapeutic intervention, the biomarker should reflect a direct effect of that medicine.
See also
- Biomarkers of aging
- Cardiac marker
- Molecular risk assessment
- Cancer biomarkers
- ROCCET
- Continuous Individualized Risk Index
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