A biomarker is a biological marker. It is an indicator to reflect and identify normal or diseased state of the body (biological state), such as organ function, progressions of a disease, and effects of treatment. They are separated into three specific types of biomarkers: biomarkers of exposure, biomarkers of effect or biomarkers of susceptibility.
There are several desired characteristics for a biomarker.
Sample collection should be simple and reliable for diagnostics. Blood, urine or saliva samples collections encompasses of technical factors such as calibration and quality assurance. Individual-related factors such as education and training of operators is needed to minimize and eliminate possible errors (during preparation of individual, sampling procedure, sampling handling and measurement) that may cause disturbance to the analysis and results.
There should be well-documented analytical procedures with defined performance characteristics and accessible records to allow verification of the results of the biomarker. The results from different laboratories should not differ significantly from each other.
Biomarkers should be specific for a particular type of exposure. A good relationship between biomarker measurements to the degree of exposure is needed so that results would not be too difficult to interpret. The results obtained from the biomarkers should also be quick so that rapid initiation of the treatment can be provided to the patient.
An example of a biomarker would be antibodies. The presence of antibodies would therefore indicate an infection within the body.
Proteomics techniques used in discovery of disease biomarkers
Provide detailed description on some of the proteomics techniques used in discovery of biomarkers
There are several techniques used in the discovery of disease biomarkers. Some examples are 2D-PAGE, mass spectrometry, SELDI-TOF, antibody microarray, tissue microarray, ELISA and western blotting.
ELISA (Enzyme-linked immunosorbent assay)
It is a quick and sensitive method used for quantitative and qualitative measurement and detection of antigen or antibody titre in a sample. There are several types of ELISA: Indirect, sandwich, competitive and reverse.
Methods to perform an antibody-capture(Indirect) ELISA, which is used to determine titre of antibody against the antigen.
The 96-well plate is coated with antigen and incubated.
Solution is discarded and plate is washed with PBS-Tween, to remove unbound antigens.
Skim-milk is added to block off non-specific binding site. Incubate.
Plate is washed with PBS-Tween again to remove excess casein.
Serum sample is added to the wells and incubated.
Wash off excess serum sample.
Add secondary antibody conjugated to an enzyme. Incubate.
Wash off excess secondary antibodies.
Apply a chemical which converts the enzyme into a color or fluorescent signal.
Measure absorbency or fluorescent of the plate wells to determine presence and quantity of the antibody using an ELISA plate reader.
Indirect ELISA can be used to determine HIV in serum donors if HIV antibodies are detected in their samples.
Disease biomarkers in cancer, cardiovascular disease, diabetes and neurological disorders
Cite some examples of disease biomarkers in each category.
Describe e.g. history use, how successful etc.
Disease biomarkers in cancer
Screening can be done to detect prostate cancer, cancer that develops within the prostate gland, at its early stage before symptoms develop. Prostate-specific antigen (PSA) blood test and digital rectal exam (DRE) can be performed easily. Almost 99% of all prostate cancer can be detected using the PSA test.
High levels of PSA, a substance made by the prostate, may indicate risk of prostate cancer. However conditions such as enlarged prostate, prostate infection, inflammation may increase levels of PSA. Age and race may also be a reason for elevated PSA levels as PSA levels tend to increase with age.
Disease biomarkers in cardiovascular disease
Cardiovascular diseases belong to a class of disease which involves the heart as well as blood vessels. Studies of cardiovascular biomarkers are able to predict the risk of cardiovascular diseases such as heart attack, stroke or cardiac arrest.
A high level of biomarkers can identify groups at risk, but it is unable to predict an individual’s risk. BNP is a 32 amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of cardiomyocytes (heart muscle cells). During a 10-year study done, high B-type natriuretic peptide (BNP) and urinary albumin content has been proved most useful in predicting future cardiovascular events.
Disease biomarkers in diabetes
Adiponectin, is a 244 amino-acid-long polypeptide, that could be used as a biomarker for type 2 diabetes. It is a protein hormone that modulates metabolic processes (metabolic hormone), such as regulating insulin levels and fatty acid catabolism. This hormone is important in the suppression of metabolic derangements that causes type 2 diabetes. Therefore high amounts of adiponectin are associated with reduced risk of obesity and type 2 diabetes.
Type 1 diabetes occurs when there is an autoimmune response of the pancreatic islets by the T-cells. This would result in the destruction of insulin production, hyperglycemia may also occur during later stages. Controlling these destructive T-cells would be essential to controlling the disease. CD40 expression is different between non-diabetic and diabetic individuals. And therefore it is being studied as a biomarker for Type 1 diabetes.
Disease biomarker neurological disease
Alzheimer’s disease is a common form of dementia. . There is currently no known cure or treatment for Alzheimer’s disease. Symptoms may include inability to acquire new memories, difficulty in remembering, confusion and long-term memory loss. Gradual loss of bodily functions would also occur, ultimately leading to death
High levels of P-tau231 are able to predict future memory decline and loss of brain gray matter in the medial temporal lobe. The medial temporal lobe is found to be vulnerable in the early stages of Alzheimer’s disease. In a study conducted, group with worsened memory had higher levels of P-tau231, which is associated with reductions in the medial temporal lobe gray matter.
