Unlocking Biomarkers: A Guide to Vital Health Indicators
Biomarker, a term that was first used in geological research, refers to geological materials and natural sediments or organic compounds from living organisms, which can be used for geological dating and environment monitoring, among other things. This term was formally introduced into the biomedical field in the 1980s. In 2001, A National Institutes of Health (NIH) working group provided a definition of a biomarker as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention". Based on this concept, a biomarker must encompass two characteristics: it is objectively measurable, and it acts as an evaluation of a process in the human body. As such, broadly speaking, a biomarker can be anatomical, histological, imaging, genetic, protein, metabolic, etc., as long as it satisfies both features. Biomarkers, in a narrow sense, are biochemical molecules derived from human tissues, such as those that exist in blood, body fluids, or tissues, which can be utilized to assist disease diagnosis, therapeutic efficacy prediction, and prognosis assessment.
There are various uses for different biomarkers: 1) Diagnostic, e.g., for diagnosing a disease status or identifying patients at risk. 2) Disease staging or severity evaluation. 3) Patient stratification, e.g., making perceptions of whether a treatment will likely be effective or ineffective. 4) Prognosis of disease, especially for assessing the survival of cancer patients. 5) Monitoring or prediction of toxicity of interventions. 6) Evaluation of therapeutic or pharmacokinetic effects. Following the development of genomics technology, beyond genetic and proteomic biomarkers, metabolomics biomarkers and other associated fundamental and clinical research have also been greatly advanced, with more and more metabolic biomarkers being reported and applied in clinical practice.
Precision medicine and individualized medical care are the hallmarks of health care in the 21st century. Precision medicine is increasingly being emphasized by the clinical medicine community, with biomarkers as the cornerstone for the implementation of precision medicine and individualized medical care. Biomarkers are a class of markers associated with cell growth, proliferation, and disease genesis, among others. They can reflect physiological or pathological processes or responses to therapeutic interventions, providing utility in early diagnosis, disease prevention, drug target identification, drug response prediction, and beyond. Finding and discovering valuable biomarkers has become a hotspot in current research.
From Exploration to Revelation: Biomarker Discovery Journey
Biomarkers are mostly described in geological literature prior to their application in biomedicine. In the 1960s, biomarkers began to appear in the medical literature, and by the 1980s, it was formally introduced into the biomedical field. It has also been described differently within biomedicine. In 1987, the U.S. National Academy of Sciences first defined biomarkers as foreign compounds that cause changes in the cytological or biochemical components and in the structure or function of an organism or sample. Benson et al. considered biomarkers as biochemical, biological, or pathological responses that arise in individual organisms, where these biological responses give information about exposure to an environmental pollutant or about sublethal effects caused by exposure.
A biomarker is a biological response of an organism to a chemical or chemicals, which can be used to measure an organism's exposure to a chemical or, in some cases, to measure the effects of certain toxic substances. The introduction of the biomarker definition signifies a clearer understanding and awareness of its importance. The decade following the introduction of this definition also marks the rapid development of high-throughput technologies such as biochips and next-generation sequencing. With the evolution of molecular biology and the concept of "omics", researchers have been able to further elucidate the pathogenesis of various diseases, generating a huge amount of biomarker data and relevant literature, which has made it possible to study biomarkers with high specificity and accuracy. Novel biomarkers have benefited from high-throughput and large-scale detection technologies, such as gene chips and widely-targeted metabolomics. The development of these assays has been accompanied by the emergence of a range of novel biomarkers.
Novel markers have their own advantages, such as novel circulating markers for tumors, circulating tumor microvesicles, and circulating tumor cells have shown great clinical value. Extracellular vesicles are important modes of intercellular signaling and play a key regulatory role in physiological or pathological conditions, representing a class of biomarkers with great promise for translating into clinical applications. A large number of studies have shown that extracellular vesicles play an important role in tumor cell growth, epithelial-mesenchymal transition, distant tumor metastasis, and induction of drug resistance. Circulating tumor cells can be detected at early tumor stages and have been shown to carry genotypes that are highly similar to those of the primary tumor tissue. Notably, the research on these new circulating biomarkers has moved from recurrence monitoring, molecular typing, and drug guidance to early diagnosis. A series of clinical trials are being conducted to validate the effect of these markers on the early diagnosis of tumors. It is believed that these markers will be of great significance to the prevention of tumors and that these novel biomarkers are bound to broader applications.
Crafting Ideal Biomarkers: The Quest for Health Insights
Biomarkers are widely utilized in biomedicine, such as disease screening, disease diagnosis, treatment selection, and evaluation of treatment efficacy. With the progress of biomarker research, the human body's own biomarkers are expected to become the basis for diagnosis and treatment and to help realize early diagnosis of diseases and personalized treatment for patients.
The advent of high-throughput technologies has greatly accelerated the output of biomarker research data, with a growing number of research projects and literature reports on biomarkers. However, one of the facts unfolding despite the huge investment is that there are still not many individual biomarkers that are sensitive and specific enough to be practically used for disease diagnosis. Combinatorial biomarkers have improved detection rates, but sometimes, the reproducibility of the test results in different populations is not satisfactory. The reason for this lies in the differences in individual genetic backgrounds, in addition to differences in detection techniques and data processing. Within some disease contexts, the baseline biomarker values vary considerably between individuals, posing problems in the determination of positive and negative test results. How to mine meaningful information from the huge amount of data and use it for biomarker development, and how to more accurately introduce ideal biomarkers with clinical significance that can withstand clinical validation, is indeed a major challenge for related research.
From the aspect of clinical practice, an ideal biomarker should possess the following characteristics: ① High specificity - a highly specific biomarker allows accurate determination of the nature of the disease, facilitating its diagnosis. ② High sensitivity - it should be able to detect the disease at an early stage and be used for disease screening. ③ Convenient sampling - biomarkers that are present in blood or body fluids and can be obtained by accessing test samples in a non-invasive manner are of greater practical value, whereas surgical or puncture procedures for acquiring specimens are invasive, limiting their applications. ④ Long half-life and easy storage - this is important for the realizability of the test and the stability and reliability of the results. Most of the biomarkers identified so far suffer from a lack of specificity or low sensitivity. As a result, a single biomarker often fails to appropriately reflect the type and stage of the disease. In other words, multiple biomarkers are combined to evaluate the onset, progression, and prognosis of the disease, among other aspects.
