The word “Biomarker” is derived from the term “Biological marker,” which is an overall marker of some biochemical, cellular, and molecular changes that can be detected in biological systems such as cells, tissues, or bodily fluids.
The development of biological indicators through these processes can assist clinical practice and biomedical technology in the early prognosis, diagnosis, and early detection of diseases including cancer and heart attacks.
So basically, a biomarker is anything that can help in the identification of disease, be it a symptomatic feature, biological process, a metabolite or a biological structure. It includes biomolecules like lipids, carbohydrates proteins, enzymes, hormones, DNA, RNA, and platelets etc.
Understanding the importance of Mortality prediction
The prediction of mortality has the potential to aid in the advancement of measures aimed at alleviating mortality rates.
The utilization of mortality prediction has demonstrated efficacy in helping clinical decision-making, resulting in improved patient outcomes and reduced cost of healthcare.
Although mortality prediction models raise questions on ethical and social justice concerns, it has reduced the mortality rate and decreased the length of stays in the ICU. So keeping ethical values, researchers and healthcare providers can assess the factors that contribute in increasing mortality, in order to improve our understanding of complex factors that lead to a decline in health.
What are Biomarkers?
Biomarkers are measures of the biological state of the body. It’s an indicating difference between abnormal or normal processes inside the body, like, if the blood pressure is higher than normal then it’s an indication of an ongoing abnormal heart condition.
Likewise, if the cells are growing uncontrollably and spreading to other parts of the body then it’s a biomarker of cancer.
So we can say that it’s simply a change from normal to abnormal or abnormal to normal biological state of the body.
They can be detected easily in a number of biological samples like blood, urine, saliva and tissue and can be helpful for early diagnosing, monitoring disease and assessing the ongoing treatment response.
In addition to their beneficial characteristics, the validation and clinical application of biomarkers requires a significant investment of time and resources, including complex clinical trials and extensive research, in order to achieve their intended clinical usefulness.
How they can be helpful in mortality prediction?
One of the biomarkers recognized as C-reactive protein is used to detect disease progression and monitoring. It is helpful for indicating disease progression as its level rises and its decreasing level is an indication towards the normal condition. So its rising level is a negative sign of health and its decreasing level towards normal is a positive sign of health condition.
Likewise, B-type natriuretic peptide (BNP) and N-terminal pro B type natriuretic peptide (NT-pro BNP biomarker) is useful in patients with heart failure. Their high levels are associated with negative signs of health and levels towards normal are considered positive signs.
So, biomarkers significantly predict future death above and beyond the demographic and self-reported health conditions.
How biomarkers are measurable in the body?
There’s no one specific substance considered as a measure of the body’s health condition but several biomarkers measure biological responses like biochemical, cellular, physiological and behavioural changes.
They serve as early warning signals for adverse effects at higher biological organization levels (community or population) indicating the unbearable levels of contamination in a certain biological organization.
On the basis of organ level system of the body, biomarkers help to identify the condition of that particular system of the body.
For example as below:
Cardiovascular biomarkers are acknowledged as substances present in the bloodstream that can indicate the presence or severity of the cardiovascular disease.
For instance, Troponin is used to identify and monitor heart attacks and Brain natriuretic peptide is used for monitoring and diagnosing heart failure.
Cancer biomarkers are specific blood components that can identify the presence or stage of cancer.
Two of these are prostate-specific antigen (PSA) and carcinoembryonic antigen are biomarkers for colon cancer.
Changes in the levels of these circulating tumors can tell the professionals about the effectiveness of treatment and may allow them to modify the care plan for better results.
These include Blood Urea Nitrogen(BUN) and Creatinine. These two biomarkers are helpful for predicting kidney function.
Albumin is another biomarker for kidney function used to assess the extent of damage caused to the kidney.
Patients having low levels of albumin are at higher risk of mortality because of renal illness.
The biomarkers specific for respiratory problems include Fractional exhaled nitric oxide(FeNO) used for diagnosing and monitoring Asthma.
Surfactant protein-D(SP-D) is used to gauge the severity of Chronic Obstructive Pulmonary disease.
Changes in the levels of these Biomarkers can be helpful for healthcare professionals to modify their treatment plans.
Biomarkers for Liver include Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) for evaluating liver function.
Also Bilirubin can be used to evaluate the extent of liver damage.
The value of Biomarkers
Precision medicine emphasizes the use of biomarkers to tailor medical treatment and prevention strategies based on an individual’s genetic, environmental, and lifestyle factors.
Due to variations in genes, environment and lifestyle this approach helps to develop personalized treatment with respect to individual differences.
It has already helped in making advances in the treatment of certain types of cancer, where targeted therapies have been developed to attack cancer cells while minimizing the damage to healthy cells.
For early detection of disease
A person’s physical state may deteriorate and show early indicators of a sickness like high blood pressure or they may show signs of an illness developing inside their body.
So these biomarkers serve as early signs of a developing condition.
An illustration of the potential usage of cardiovascular biomarkers is their use in the early detection of cardiovascular disease. Troponin, for instance, is a biomarker that can be employed in monitoring and diagnosing heart attack, while Brain natriuretic peptide is useful in diagnosing heart failure.
Personalized treatment plans
As discussed above, precision medicine could be a key to the personalized treatment plan. As this approach takes into account variations in genetics, environment and lifestyle factors to create individualized treatment plans and strategies. So each individual benefits from its advancements.
The individualization of patient care has been a longstanding objective of medicine. As previously mentioned, precision medicine has the potential to serve as a crucial component in the development of individualized treatment strategies.
The proposed methodology considers the interplay of genetic, environmental, and lifestyle factors to develop personalized treatment plans and methods, given the distinctive biomarker profile of each patient. Each individual derives benefits from the advancements made.
Biomarkers have been developed for personalized therapy in cancer, as the development of targeted therapies have opened up a paradigm of precision medicine by using biomarkers.
A significant challenge in the biomarker field is to differentiate between a reliable biomarker and a potential biomarker that could have widespread utility in informing critical clinical and commercial determinations.
A reliable biomarker is one that is currently exhibiting optimal performance in prognostication, diagnosis, and disease monitoring, whereas a potential biomarker is one that has not yet demonstrated clinical efficacy and necessitates further investigation.
With the increasing need to address quality and suitability of biomarkers, a concept of biomarker validation and qualification have been developed.
Various challenges faced for the development of biomarkers include:
• Variability among age, sex, lifestyle, genetics and disease status.
• Lack of standardization in biomarker measurement and assays lead to inconsistent results across different laboratories.
• Costly development and validation of biomarkers.
• Specificity of biomarkers to the disease and condition for which they are measured
• Legal and ethical issues
Let’s discuss two of these!
Accuracy and reliability of biomarkers
The precision of a biomarker is evaluated by considering the scenario in which two distinct methodologies yield different results for a given target. How would one determine which assay is yielding accurate results? Ensuring accuracy is crucial in achieving the correct outcome, particularly in avoiding the prescription of unnecessary medication to healthy individuals and in appropriately treating patients with the disease.
So these above are the challenges that scientists face every day for biomarker assay.
Another consideration in biomarker assay is its association with diagnostic medicine. It is defined as the ability of a test to correctly identify the patient with a disease.
It is believed that accuracy is more than just trueness, so additional experiment for assessing the accuracy must be appreciated, that can complement a traditional spiked recovery experiment.
Cost and accessibility of biomarkers
The efficiency and cost of healthcare tests is dependent upon a variety of factors, including the specific testing methods and standards of measurement employed, as well as the healthcare system within which they are used.
The economic viability of healthcare treatments seems to be based upon enhancing patient outcomes and mitigating the overall expenses of healthcare.
Some biomarkers just require simple blood testing that may be relatively inexpensive while others may require imaging techniques and genetic analysis.
An additional factor to be taken into account is the requirement of certain biomarkers for non-invasive testing methods, such as urine or saliva, which can enhance patient accessibility and reduce overall costs. Conversely, other biomarkers may necessitate invasive procedures for sample collection, thereby increasing expenses.
Current developments in biomarker research
Tears are a numerous combination of proteins, electrolytes, and water. Alterations in their composition may serve as an indication of medical conditions, thereby enabling the detection of diverse ocular and systemic ailments, such as infections, allergies, and certain forms of cancer. The field of biomarker research is currently experiencing growth and expansion. The proteome of tears presents a substantial reservoir of biomarkers that can be utilised for diagnostic purposes.
The collection of tear samples is a convenient, rapid, and non-intrusive procedure for patients. The continuous progress in proteomic technology has enabled the detection, identification, and quantification of biomarkers in tear fluid from small sample volumes. There are several methods available for collecting samples, including the use of a paper strip to collect tears from the lower eyelid or a small tube.
The specimen may be subjected to analysis for the presence of inflammatory cytokines, proteins, and growth factors.
Furthermore, alterations in the concentrations and composition of the tear components may indicate not only modifications to the ocular surface but also pathophysiological variations in other tissues and organs.
Various proteomic methodologies have been firmly established and implemented in the identification of biomarkers in tears. However, it is important to note that each technique has its own set of limitations. The utilization of gel-based techniques for the identification of novel protein biomarkers presents both benefits and drawbacks.
On the one hand, the data given applies to the proteins identified, covering the point at which they are molecular mass, and the existence of post-translational modifications.
In contrast, it should be noted that non-MS-based techniques exhibit a greater limit of detection relative to MS (Mass spectrometry)-based techniques, which consequently renders them incapable of detecting proteins present in low abundance (ranging from picograms to nanograms).
MS-based techniques present challenges in the observation of PTM (post-translational modification) changes of proteins, yet they offer a wider proteome range coverage compared to gel-based techniques. The biomarkers that have been identified through the utilization of both techniques will necessitate additional validation and quantification.
Multiplex techniques that rely on antibodies exhibit specificity; however, they necessitate a prior identification of the analytes that are to be detected in the sample.
To mine tear biomarkers and determine their sensitivity and specificity, it is essential to develop a well-defined tear collection procedure, analyze data to determine an appropriate sample size, and use quantitative methods with consistent reproducibility across independent laboratories.
It is improbable that an isolated biomarker would possess the necessary specificity and sensitivity to effectively diagnose most systemic or ocular ailments, including cancer and dry eye. Therefore, it is recommended that future tear biomarker research should primarily concentrate on exploring biomarker panels that are specific to particular diseases.
Future of biomarkers
With the growing Artificial Intelligence day by day, biomarkers in the future will be utilizing artificial intelligence and machine learning, leading to the discovery of more accurate biomarkers and produce better treatment results, also improving the diagnostics while using large datasets of biomarker information.
Future data collection is crucial. Annual doctor visits are thought to be difficult. Can health monitoring be improved? Many studies suggest liquid biopsies are a potential study area. Why is a urine sample required at a hospital? Home toilets may eventually include automatic biomarker detection devices. Home toilets monitor health metrics everyday. The toilet system warns about questionable urine discoveries. The tool will advise on a timely medical care.
Digital Health Technologies (DHT):
Digitization has improved medical research, diagnosis, and therapy during the past decade. Digitization boosted DHT development and uptake by consumers, researchers, and providers. These technologies enable outside-clinic health data collecting. Digitalization has made the term “digital biomarker” widespread in healthcare, covering many parameters. Biomarkers and clinical outcome assessments have the potential to explain medical conditions.
The utilisation of digital health technologies, such as smart watches, has become prevalent on a global scale. These devices are capable of monitoring fitness metrics and offering valuable insights into an individual’s overall health. Specifically, they are currently being employed to measure heart rate, blood pressure, and physical activity levels.
The utilisation of voice and typing characteristics on mobile devices can provide valuable insights into an individual’s mental health status. Consequently, mobile applications can leverage this information to evaluate and monitor an individual’s mental health.
With modern healthcare digitisation, non-biological extrinsic factors like pollen count may predict and influence health. However, methodical scientific proof is required.
In the future there will be more advanced techniques for early detection of a disease and tailored treatments to individuals based on their unique biomarker profile. So reducing healthcare costs by targeting the treatments just to those patients who are more likely to benefit from it.
WHAT IS THE SINGLE BEST PREDICTOR OF MORTALITY RATE?
It has not been yet possible to predict mortality with a single biomarker, but several biomarkers together can predict the mortality such as lifestyle, age and sex can contribute together in predicting the mortality.
One of the recent study examined that combination of multiple biomarkers for determining cardiovascular health can serve as predictive value. It has been found that combination of several biomarkers such as cystatin (Biomarker of kidney function), Brain natriuretic peptide (BNP) for heart function and C-REACTIVE protein (CRP) has proven to be more predictive of mortality than any single biomarker.
WHAT ARE COMMON MORTALITY INDICATORS?
Common mortality indicators include high blood pressure, diabetes, smoking, age and gender. These indicators help healthcare professionals to create preventative measures in order to improve better treatment result on the basis of personalized treatment plans.
WHAT ARE THE 5 BIOMARKERS OF LONGEVITY?
These Include Biomarkers that Are Predictable not of mortality, But predictable of Long Lifespan.
But Still There Is Ongoing Research On These Biomarkers Of Longevity. Some Of These Include:
- C-reactive Protein (Crp), Which Is A Marker Of Inflammation Us Associated With Many Age Related Diseases. So Low Levels of this are Indicative Of Long Lifespan.
- Length Of Telomere, Which Is A Cap On The Ends Of Chromosomes, Shortens With Age. Longer Lengths Of These Caps On Chromosomes Are Associated With Increased Lifespan And Healthy Aging.
Some of these biomarkers are indicative of longevity rather than mortality. However, research on these biomarkers of longevity is currently ongoing.
Several biomarkers have been identified to be associated with age-related diseases, among which is C-reactive protein (CRP) that serves as an indicator of inflammation.
Low levels of this substance are indicative of a prolonged lifespan.
Telomere length :
The telomere length, which serves as a protective cap on the terminal regions of chromosomes, undergoes a reduction in size as an individual ages. Extended lengths of these caps located on chromosomes have been found to be correlated with enhanced longevity and healthy ageing.
Chronic inflammation has been linked to age-related diseases. Interleukin 6 (IL-6), a cytokine that plays a role in chronic inflammation, may serve as a biomarker to indicate the presence of inflammation within the body.
Blood lipid levels:
Given the significant impact of cholesterol on cardiovascular health, it is widely acknowledged that elevated levels of high-density lipoprotein (HDL) and reduced levels of low-density lipoprotein (LDL) are indicative of improved cardiac function and increased longevity.
Mitochondria are organelles located within the cell that serve as the powerhouse of the cell. Enhanced mitochondrial function is correlated with a prolonged lifespan, while the impaired mitochondrial function is linked to the process of aging and age-related ailments.
In conclusion, biomarkers can be helpful for predicting mortality earlier and earlier detection of disease for prevention. They are also promising for providing predictions on longevity or healthy aging.
Further research is vital to enhance the precision of techniques and reduce the cost of biomarkers for diseases that demand a significant volume of biomarkers. Thus, ensuring that the resources are available to individuals who may obtain advantages from them.
1: D. D. Zhang and T. P. Shanley edited “Biomarkers in Medicine, Drug Discovery, and Environmental Health” (Wiley-Blackwell, 2010).
2: J. N. H. Venter and J. H. Powers edited “Biomarkers in Clinical Drug Development” (Humana Press, 2011).
3: M. A. Hayat edited “Biomarkers in Cancer: Diagnosis, Treatment, and Prognosis” (Springer, 2013).
4: R. R. Tice and I. G. Sipes edited the book “Biomarkers in Toxicology” (Academic Press, 2014).