Scientific Novelty and Significance of the Program

Literature data indicates that significant progress has been noticed in the field of biomedical technologies. Innovative technologies have been introduced in the field of laboratory diagnostics; personalized and translational medicine is developing in various groups of diseases, including malignant neoplasms. The emergence of new, technologically advanced capabilities for conducting immunohistochemical and molecular-cytogenetic studies in the diagnosis of oncological diseases, including neurooncological ones, have contributed to the development of targeted therapy with the use of targeted drugs, which led to an increase of the patients’ life.

It is necessary to create a biobank with biobanking of tumor samples of the central nervous system and venous blood components of neurooncological patients for the further development of immunohistochemical and molecular cytogenetic studies and the development of the new directions in therapy (targeted therapy, pharmacogenomics) and neurosciences. The creation of an electronic biobank of tumors of the central nervous system is an important and very urgent task in the era of personalized medicine, which carries the main goal of the development of neurosciences [6, 7]. The main starting points for resolving issues related to the biobank were the messages of the President of the Republic of Kazakhstan, discussions of the deputies of the Mazhilis of the Parliament, the State Program for the Development of Healthcare of the Republic of Kazakhstan for 2020-2025 and amendments to the Code "On the Health of the People and the Healthcare System" [1, 2, 3, 9].

International cooperation plays an important role in the development of biobanking with its high costs in the creation and maintenance of functioning and the collection of biomaterials. The composition and volume of biobanks around the world remain different, depending on the priority of scientific research. There are already many of the large centralized biobanks: several dozens of large biobanks and several hundreds of small ones in most of the developed countries in the world such as Korea, Sweden, USA, UK, etc. For example, the national biobank of Korea is integrated with 17 regional biobanks and contains more than 525 thousand of samples of various areas (blood serum, plasma, DNA, etc.) [14]. The Swedish National Biobanking Program ensures the conservation of 3-4 million biosamples, which were obtained annually during the routine medical examinations [7]. One of the largest biobanks is the US Department of Defense Serum Repository [8]. The biobank began to take a shape about thirty years ago as a “by-product” of HIV monitoring of military personnel. Since then, blood samples, which were left after testing for HIV, were sent to the storage, and now, 55.5 million of samples from 10 million people have been accumulated. In addition to the routine functions of monitoring infectious diseases and drawing up "health profiles", the biobank is used for a number of scientific programs, including the study of population genetics and predisposition to certain diseases.

It should be noted that one of the first biobank projects was the Framingham Heart Study project, which was started in 1948 in the United States of America. Then, 52 families took part in the study with a total number of more than 5 thousand individuals [12,13].

The biobank of tumors of the central nervous system will be aimed at the development of various areas of neuroscience, personalized and translational medicine. The development of translational medicine will make it possible to quickly transfer the results of fundamental research (mainly in the field of molecular cytogenetics and biochemistry) into clinical practice, which will make this area especially promising and demanding. The created biobank will expand and thereby develop personalized medicine, scientific activity in this direction, which will give a powerful impetus to the industry in order to comply with generally accepted standards of developed countries of the world.

Diagnostics of tumors of the central nervous system is a very difficult task. In the process of diagnostics, not only the pathohistological structure of the tumor is taken into account, but also the most significant molecular genetic changes and chromosomal aberrations in a tumor cell. The results of recent studies have shown the important role of a number of genetic mutations in the development and progression of gliomas where mutations in the isocitrate dehydrogenase (IDH) gene occupy a special place [10, 11]. The frequency of IDH mutations in diffuse grade of II and III gliomas is 60-90%, 80-85% in secondary glioblastomas, and <5% in primary glioblastomas. Mutations in the IDH1 gene are the most common (over 90% of all IDH mutations) [10]. Due to such a high frequency, the mutant IDH1 gene is referred to as markers of gliomogenesis [11]. Thus, a mutation in the IDH gene plays an important role in the diagnosis of the degree of malignancy of gliomas. It has a prognostic significance - the presence of an IDH mutation indicates a more favorable outcome of the disease and demonstrates higher overall survival rates.

Earlier, JSC "National Center for Neurosurgery" conducted a study of IDH mutations of patients with brain gliomas, as well as analyzed clinical parameters and laboratory markers of blood inflammation, depending on its presence. The IDH mutation was identified in 94 cases (49%). Correlations were found between the presence of an IDH mutation and an increase in observations with epileptic syndrome, as well as a decreased level of markers of blood inflammation: C-reactive protein - CRP, the ratio of neutrophils to lymphocytes – NLR and the ratio of platelets to lymphocytes - PLR. At the same time, a strong correlation was shown between NLR, PLR and CRP. The only factor among the studied blood parameters that did not have a statistically significant relationship with epileptic syndrome was the indicator of erythrocyte anisocytosis - RDW. Thus, we assumed that the relatively favorable prognosis for epileptic syndrome of patients with brain gliomas is associated with the IDH1 mutation, which leads to a decrease in the level of blood inflammation.

After conducting a literature review, we have identified many studies that examined potential pathomorphological, proliferative and molecular markers that are associated with aggressive clinical manifestations and will provide a more accurate prognosis for patients with gliomas. Molecular changes deserve special attention: CDKN2A / B point mutation, CDKN2A / B promoter methylation, CDK4 amplification, homozygous RB1 deletion, CDK6 amplification, PIK3R1 mutation, PIK3CA mutation, PDGFRA amplification.

Molecular chaperones, in particular the Hsp70 protein, perform important intracellular functions, including participation in the assembly of polypeptide chains, regulation of apoptosis and autophagy. Considering their key protective value for cell physiology, an increased expression of chaperones is observed in cancer cells, which correlates with a poor prognosis for the survival of cancer patients. The development of diagnostic panels for the expression of chaperones (for example, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90) in brain neoplasms will make it possible to stratify patients and, in the future, create individual therapy regimens based on the suppression of certain representatives of the chaperone families.

We will study whether there are thresholds of proliferative activity based on the number of mitoses in cells, the level of the proliferative index Ki-67, or other pathomorphological features typical for glial tumors that can correlate with the outcome of the disease and improve modern diagnostic criteria, the results of these studies will be digitized.

To date, molecular cytogenetic studies in the RK are actively used in perinatology in the diagnosis of hereditary and genetically determined diseases, hematology and general oncology. The issues of molecular-cytogenetic research in neurooncology in the RK remain unresolved.

In modern neurosurgery, along with the main diagnostics of brain tumor diseases using anatomical magnetic resonance imaging, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are actively used, which allow you to get more information about the pathological focus in the functional mode. Functional magnetic resonance imaging with cognitive tasks has shown an advantage in the preoperative assessment of a patient with brain tumors to minimize the consequences of surgery and postoperative recovery [15,16,17,18].

The use of preoperative fMRI mapping of linguistic zones showed a decrease in the time spent during intraoperative functional monitoring, and, in general, increased the effectiveness of treatment for brain tumors in the area of linguistic functions [19].

At the moment, the diagnostics of tumors of the central nervous system is a difficult task  for doctors of pathologists. The creation and improvement of a modern pathomorphological laboratory with a biobank and digitalization of all types of research will contribute for improving the quality of diagnostics of tumors of the central nervous system and the development of science and statistics in neurooncology. The result of the created modern pathomorphological laboratory can be the creation of a reference neuropathomorphological laboratory of the Republic of Kazakhstan based on the Pathological Department of JSC "National Center for Neurosurgery".

Diffusion and widespread digitalization requires the generation of patient data in a single digital repository. This makes it possible to combine the existing data asset into a digital biobank for more convenient set of data, which can be, then, automatically requested and analyzed.

The electronic biobank in the era of personalized medicine carries the main goal of developing the research potential and biosecurity of the country. The electronic biobank is a unique and modern platform for attracting investments, both foreign and domestic, with the aim of developing science, clinics and diagnostics of tumors of the central nervous system.