Biomarker: Biological imprints and solutions for future diagnosis and therapy

Definition and needs of biomarker:

Biomarker or ' biomarkers ' are molecules that represent a biological data. Biomarker may be merely a chemical, such as glucose as a marker of diabetes, or a protein molecule like antibodies, which is a marker of infection, and a gene or DNA marker is a marker for inter Genetics. With the development of biochemical techniques capable of studying many molecules on the same sample as microarray, proteonomics, biomarker is often a group of genes or proteins of biological data.

Pathologically, unlike pathogen agents described in molecular form such as genes or bacteria are pathogenic causes, biomarkers are just " symbols " of the disease. These manifestations include all cell changes related to the pathology. Thus, biomarkers include pathogenic molecules and molecules created after the disease develops.

Biomarker is also known as the " signature " of a biological phenomenon, recent studies have demonstrated the usefulness of biomarker for many biological disciplines from research to application. The biomarker researchers believe that the biological signature contains pathological mysteries, so the search for the parasite will help achieve results that are effective and effective in medicine. These applications include accurate diagnostic methods for complex diseases involving multiple genes (cancer, diabetes, cardiovascular, neurological .), or immune, genetic, and infectious diseases. or disease due to environmental factors. Biomarker also has many expectations in the application of measuring drug effects.

We often know many discoveries of genes and pathology, but in fact the application of these genes for diagnosis and treatment is very limited and limited. On the SHVN forum, the limited use of genes in pathology is mentioned from the article of Dr. Nguyen Van Tuan (number 14/08/2006). The limit of gene use in diagnosis can be summarized as Dr. Tuan wrote: 'Except for some genetic diseases that genes play an important role in diagnosis, most chronic diseases such as Diabetes, cancer, heart disease, complications, osteoporosis, etc., the gene does not play an important role as many people think. Genetic diagnosis for these diseases cannot therefore benefit patients. ' There are two main reasons for this limit. First , most genes are related to genetics with very low frequency in the biodiversity population; secondly , all diseases have the participation of a gene complex, which is largely unknown, not from a gene.

For these reasons, biomarker has been one of the key researches of biomedical over the years, and there have been results showing the importance of biomarker in bringing gene application to disease diagnosis. as well as many other medical and scientific aspects. The diagnostic applications of biomarker outlined below show a great correlation of biomarker in many sectors of biology. It is difficult to present every aspect of biomarker in this article limit

Model of diagnostic application of biomarker in many biological branches.

Research method of biomarker:

As mentioned above, biomarker includes many forms, from chemicals to genes and proteins. The biomarker tracing methods mainly detect protein molecules, because proteins are the final product of genes and directly affect biological phenomena. The more important reason is that proteins are the most abundant biological component of the cell compared to mRNA or beyond. A gene can have multiple mRNA copies and the translation cycle (translation) and changes after translation (post translational modification) of copies often produce more protein than mRNA copies.

According to current estimates, there are between 300,000 and 500,000 proteins from about 30,000 genes of the human genome . This abundance of form and amount of protein will be the hallmarks that highlight the difference in cell biology when there is a change. Some research groups use gene expression profile as biomarker, or combine protein and RNA, DNA for greater accuracy, but of course will also be more complicated. Recently, the phenomenon of methylation of DNA and RNAi is also a new object of biomarker research because of their important role in regulating gene function related to pathology.

In principle, finding biomarkers is much simpler than finding pathological genes. Unlike genetic and pathological studies, biomarker does not require to understand the often complex mechanism of disease models. By definition, biomarkers are all changes that are expressed by the cell from one biological state to another. Talking about disease, biomarkers are all proteins that change from normal to pathological. Therefore, the exact method of biomarker determination is based on two technical steps: protein extraction and comparison of protein changes in the samples.

In terms of practicality, the search for biomarker through some periods and difficulties has not been resolved because of the new nature of this science. The main stages include:

- Refining protein of samples : Many biomarker studies need to refine samples to enrich (enrich) protein levels related to biomarker. Purification aims to remove high-protein proteins and often does not have an important pathological role such as serum albumin in the blood, cellular proteins such as actin and tubulin. Protein purification can be accomplished by a variety of biochemical methods such as chromatography, or using monoclonal antibodies to remove proteins. Protein enrichment is technically important, research from cellular biological processes and pathology suggests functional proteins are often expressed at very low concentrations, nM. compared with mM, of structural proteins or transport (carier proteins).

- Methods of extracting and analyzing proteins : There are many protein extraction methods applied to start searching for biomarker. These methods are intended to isolate the different proteins between two biological cases. Chromatography column, and two-dimensional protein electrophoresis (2 D gel electrophoresis protein) are two common methods. Column chromatography method of acid or alkaline ions for extracting proteins based on acid and alkaline properties; or based on hydrophyllic or hydrophobic. The bidirectional protein electrophoresis method can help compare protein differences based on molecular weight and charge (charges) of proteins. Both column chromatography and electrophoresis methods have drawbacks as the amount of protein analyzed is very limited. Two-way electrophoresis can only analyze between 2,000 and 10,000 proteins per dielectric; We know it's a very small number compared to the total number of proteins that can be between 300,000 and 500,000 molecules in the cell.

In studies of post-genome, proteomics industry plus mass spectrometry have made breakthroughs for biomarker research. This technique is also known as Mass-Proteonomic-based Approach. In this technique, the protein is ionized to separate from the sample complexes, and then the protein molecules will be broken down into small pieces and spread on a graph of peptide fragments arranged by weight ratio. and electric charge. The proteins on the chart are compared to the protein data established from the proteomics and from there the type and structure of the protein will be determined accurately. Comparing the histogram of proteins from pathological samples and proteins from non-carrier samples will require a specialized computer system (such as Correlogic Systems, Inc. used in NIH) to identify some proteins that are capable of biomarkers. of disease. Samples can be blood, cells, tissues, or excretions from the glands. With the capabilities of the current mass spectrometer, biomarker experiments can identify thousands of proteins from a small amount of sample such as a drop of blood. The determination of the value of these biomarkers will require a large scale clinical and statistical research program.

The achievements of biomarker research:

Because of the scientific value of biomarker, the study of this topic has been implemented in many biological and medical research centers in many countries. Technically, diagnostic firms such as Roche, Chiron, and Abbott have broad directions for biomarker research; In addition, biomarker biotechnology firms such as Ciphergene Biosystem, Pathway Diagnostics, Thirdwave, and Digene are on the rise. Especially with the major pharmaceutical industry groups such as Pfizer, Novartis, Bristol Meyers, biomarkers are being used in conjunction with essential experiments such as toxicology, pharmacology in the forestry valuation process. sieve of pharmaceuticals.

From the research of biomarker in many research centers, there have been promising results of very good applications of biomarker for the diagnosis of diseases and treatment. Completing or replacing routine biomarker applications will only be a matter of time. These biomarkers are intended to help predict and correct early cases of diseases from cancer to cardiovascular and metabolic; The biomarker is also worth predicting the effects of drugs to help health professionals make the best decisions for treating patients. Going further, biomarker has the potential to be applied in personalized medicine.

There are a lot of biomarkers found from research programs in the centers as well as pharmaceutical companies around the world. Results from the US Institute of Health Research (NIH) collected 14 proteins that could be used as a biomarker for breast cancer from mass spectrometry analyzes with breast milk samples. In the groups tested, the accuracy of these biomarkers is very high compared to the use of BRCA genes (BRCA is the gene for genetic breast cancer found in the breast cancer genome; however, this gene is only available). low incidence of 2-5% of this disease when diagnosed in the public); several other biomarker proteins have also been discovered from the study of prostate cancer (prostate), lung cancer (lung), bladder, and ovarian (ovarian) cancer; There are several recommended biomarker proteins involved in arteriosclerosis (arterosclerosis). As many results from other research centers, these NIH biomarkers have been discovered from a limited number of specimens, and are also subject to extensive clinical and statistical trials to assess the correlation. (frequency) in the masses.

The problem needs complete for biomarker application

As we know, biomarker is a collective of some genes or proteins that represent a state of biological change. As mentioned above, the foundation of Biomarker research is based on proteins, so the role of proteomics research is essential. However large numbers (anticipated between 300,000 and 500,000 proteins), and especially the complex nature of protein, are a major obstacle to biomarker studies. Aware of these obstacles and the importance of biomarker, the US National Institutes of Health Research (NIH) has set up a program with a budget of over $ 100 million to deal with problems and promote progress. set of proteomics. The purpose of this program is to: Establish and sponsor a network to link laboratories around the world to study proteomics; Synchronize and complete the techniques and methods of proteomics for this research network. Synchronization is technically important because, in fact, there are often differences in the number of biomarkers obtained from different laboratories even for the same disease. Collected from the literature, there are approximately 1,500 biomarker proteins related to cancer and, of course, the diagnosis of these proteins is necessary to select proteins of application value. Technical factors include reagents, antibodies, peptides; Sample management, and especially the method of extracting and analyzing proteins. Linking a network of laboratories aims to create a biomarker (consortium) for pathologies and biological topics.

Researchers anticipate that the biomarker database will play a crucial role in diagnosing and treating diseases in the near future. More importantly, they also believe that when combining research disciplines including bioinformatics, genomics, evidence based medicine, biomaker will help to create cell molecular models about pathology can be investigated by specific experiments from biomarker proteins. And this is the biomarker path that is likely to lead to the identification of genes that play a major role in the complex pathology of multiple genes, rather than just being expressed as manifestations. Since then, the role of genes for diagnosis and therapy will be clearly confirmed as the medical and social community has always expected.

Regarding the application, it can be said that the value of biomarker in diagnosis and therapy has been determined on a scientific level. However, the reality will require detailed clinical trials and may also be long-term, before implementing a valuable product in the social community. In addition, in order to effectively use biomarkers, it is necessary to systematically train biomarker scientific information to medical circles including doctors and testers.

Research ability and benefits of biomarker application in Vietnam:

In neo-biology studies, biomarker is highly feasible and applicable in the current research environment in Vietnam. High feasibility because as mentioned above, biomarker does not require challenging research steps such as pathological-related gene tracing, or the creation of therapeutic protein products, often technically demanding vaccines. High, elaborate and expensive. The main equipment of biomarker research is mass spectrometry plus the ability to use computer programs on proteonomics. Of course, both of these techniques need to be taken care of by professionals. In addition, as with other sciences, the program coordinator is a scientist with high inference on biological topics to analyze data obtained from biomarker research.

It is very exciting because there are biomarker studies in Vietnam now. In fact, Vietnam has advantages compared to research centers in advanced countries. These advantages include plentiful amounts of samples and a wide range of diseases; These are essential elements for statistics to obtain high-precision biomarkers by identifying and eliminating proteins in the biomarker group. In addition, Vietnam also has abundant clinical data which plays an important role in assessing the applicability of biomarker in therapy. But the most important point is the specific value of race-related biomarker; There are many clinical facts as well as folk experiences that show the high frequency of diseases that occur in Vietnamese people when compared to other races. The determination of the ethnicity's 'biological imprints' promises practical applications that bring high-quality, effective health services to the pants. These imprints will also be an important topic for medical research from pathological to environmental impact, as well as pharmacology in the search for or evaluation of the therapeutic properties of pharmaceuticals in Vietnam. .

Thai Son NDT - Tokyo Jan. 02, 2007

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