Yellow fever virus (YFV), transmitted by Aedes aegypti mosquitoes, poses a serious threat to public health in the countries of tropical and subtropical regions, as well as causes a concern in the countries with a temperate climate. The virus provokes severe symptoms, including fever, jaundice, and damage to internal organs, and the mortality rate from the infection reaches 20–60
Purpose. Accurate detection of herpes simplex virus (HSV) in ocular infections, particularly in herpetic keratitis (HSK), is essential for effective clinical management. This study compared the analytical and clinical performance of loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR) for detecting HSV DNA in corneal specimens from patients with varying clinical presentations. Methods. The analytical sensitivity of LAMP and PCR was initially evaluated using serial dilutions of HSV-1 viral stock. Clinical testing was performed on two types of corneal samples from 92 adult patients. The first group, the clinical manifestation group (n = 53), included patients with ocular symptoms but no epithelial defects, with specimens obtained through corneal surface swabbing. The second group, the keratitis group (n = 39), comprised patients with confirmed HSK characterized by epithelial loss, with specimens collected via corneal scraping. The keratitis cases were further divided into epithelial, stromal (including ulcerative and non-ulcerative), and unspecified subtypes based on a retrospective review of clinical documentation. All samples were analyzed using both LAMP and PCR methods. Results. Analytical sensitivity testing showed detection limits of ≥10 infectious units (IU) for LAMP and ≥25 IU for PCR. Across the clinical cohorts, the proportion of patients positive by both LAMP and PCR was approximately threefold higher in the keratitis group than in the clinical manifestation group (43.6
The development of molecular testing techniques has transformed the diagnosis of influenza viruses by tackling the problems caused by zoonotic spillovers, genetic reassortment, and antigenic drift. Direct use of molecular techniques to clinical data is crucial for influenza virus surveillance and diagnosis. Many laboratories now use molecular diagnostic techniques that enable prompt and precise influenza diagnosis. Even quicker detection of viral infections, including influenza viruses, in clinical samples should be possible with the combination of real-time PCR and automated nucleic acid purification. Rapid and precise identification and subtyping of influenza viruses is essential for surveillance, outbreak management, diagnosis, and treatment. This is further highlighted by the 2009 pandemic of the H1N1 of swine origin and the ongoing spread of the highly pathogenic avian influenza A virus H5N1. Even though they are fundamental, traditional techniques including virus isolation, the hemagglutination inhibition test, and the microneutralization assay are time-consuming and slow. Viral genomic material can be detected quickly and with unparalleled accuracy thanks to the great sensitivity and specificity of molecular techniques like RT-PCR, the current gold standard. Advances in molecular diagnostics, like as digital PCR, real-time quantitative PCR, and isothermal techniques like LAMP, improve the accessibility and effectiveness of detection. New technologies like electrochemical biosensors and CRISPR-based instruments offer quick, portable outbreak control solutions sanger sequencing and next-generation sequencing are two methods that provide thorough genomic insights that are essential for vaccine development and surveillance. Digital platform advancements, like as GISAID, facilitate phylogenetic analysis and worldwide data exchange, strengthening pandemic preparedness. By connecting laboratory capabilities with field applications for efficient influenza surveillance and control, these technologies continue to influence the diagnostic landscape despite obstacles related to cost and accessibility. This review cover most widely used molecular methods for testing and detecting influenza viruses as well as digital influenza management tools.
Dengue virus, Yellow fever virus and Zika virus are the arboviruses transmitted by the common arthropod vector Aedes aegypti. These three viruses belong to Flaviviridae family and show mild to severe infections in infected individuals all over the world. Approximately 400 million people are infected with Flaviviridae and more than 1 million die every year. In spite of their existence for more than a decade, there are still gaps at molecular level in understanding the pathogenesis, transmission of flaviviruses, the biology of virus-vector and the virus-host interactions. In the present study, bio computational analysis has been done on both the genomics and proteomics data of the structural and non-structural proteins of these 3 viruses. The high conservation of the fusion loop in EDII underscores its potential as a universal antiviral target, whereas the divergence in EDIII supports its use in virus-specific diagnosis and vaccine designing. The stem and transmembrane regions of EDI demonstrate structural conservation, suggesting their suitability for broad-spectrum therapeutic strategies. In the transmembrane domain, the motif SGVWTMKIGIG in ZIKV replaces SGVWTMKIGIILT in DENV, indicating length and hydrophobicity differences that may affect E protein anchoring or membrane fluidity. The interaction of DENV and ZIKV EDIII with 4–5 receptors on human host indicates strong transmission and virulence capacity of the virus by any means, compared to presence of only 1 or 2 receptors for YFV which made it easy for the researchers to develop vaccine at a much early stage and also is efficient to provide immunity against YFV.
Introduction. Recently, data accumulated during the COVID-19 pandemic are a subject of thorough analysis and numerous publications of domestic and foreign authors. The present work presents the results of a retrospective study of the peculiarities of infection with the SARS-CoV-2 virus and efficiency of the protective effect of Sputnik V vaccination/revaccination in a group of employees of non-infectious medical center during different periods of the pandemic.Materials and Methods. The study group consisted of 1506 individuals. Information on the presence/absence of the disease was registered according to PCR test data (1404 individuals), by the presence of antibodies to determinants of the SARS-CoV-2 Spike protein (74 individuals), by the presence of characteristic traits of lung damage according to the results of computed tomography (28 individuals). Information about the vaccination/revaccination dates was obtained from the questionnaire data. The results were processed in the Statistica 12.5 (StatSoft) program. Results. The morbidity and effectiveness of the Sputnik V vaccine protective effect were assessed in dynamics during the period from the beginning of SARS-CoV-2 coronavirus pandemic in Russia and, in fact, until its completion. The effectiveness of vaccination was 92.72
The etiology and pathogenesis of gender dysphoria (GD) remain unclear. Psychosocial theories put forward at the end of the last century have not received empirical support. Studies of monozygotic twin pairs concordant for gender dysphoria suggest that GD is largely (23 to 33
The aim of the study was to analyze comparatively the structure and prevalence of pathogenicity, drug resistance, and persistence genes among non-toxigenic Vibrio cholerae O1 biovar El Tor strains of different phylogenetic lineages. Materials and Methods. Nucleotide sequences of complete genomes of 233 toxigenic and 58 non-toxigenic strains of cholera vibrios were analyzed. For multilocus sequence typing of the strains, the MLST 2.0 (Multilocus Sequence Typing) online service on CGE (Center Genomic Epidemiology) platform was used, analyzing the sequences of seven “housekeeping” genes: adk, gyrB, mdhI, metE, pntA, purM, and pyrC. Phylogenetic analysis was performed using the MrBayes v.3.2.7a program based on SNP matrix obtained using the Snippy program. Results. New genomic features of non-toxigenic V. cholerae El Tor strains with the ctxAB−tcpA+ and ctxAB−tcpA− genotypes, belonging to the L3 and L4 phylogenetic lineages, were identified. A significant variability in various pathogenicity and persistence genes of non-toxigenic ctxA−tcpA− (L4) strains was found. The persistence genes localized in the composition of VPI-2 pathogenicity island genome, as well as the genes involved in biofilm formation, were the most variable. Significant genetic differences between ctxAB−tcpA+ strains of the L3 lineage were revealed. It was established that a number of non-toxigenic strains have a significant genetic similarity with toxigenic ones by the ST type, the presence of ICE and VSP-II mobile elements, allelic profile of pathogenicity genes (tcpA, rtxA), and drug resistance genes (gyrA and parC), as well as the presence of the VC2346 gene, and are apparently derivatives of typical or genetically modified cholera strains. Phylogenetic analysis confirmed a pronounced genetic proximity of these isolates to toxigenic ones and demonstrated their belonging to the phylogenetic lineage of epidemically dangerous L2 strains. Conclusions. A high level of persistence gene polymorphism underlies the extensive genetic diversity of non-toxigenic ctxA−tcpA− strains and can determine a high population adaptability to changing environmental conditions. The strains with genetic markers of the cholera pathogen were detected among non-toxigenic vibrios ctxAB−tcpA+, which indicates their origin from toxigenic strains and the need to develop diagnostic tools for differentiating non-toxigenic strains with different pathogenic potential.
The article briefly discusses the features of the immune system during carcinogenesis and the causes of its loss of cancer control. A bioinformatic approach is proposed to search for nonapeptides (immune epitopes) recognized by the main histocompatibility complex type I in the primary structure of cancer-associated proteins. It fundamentally differs from other immunoinformative tools for determining immune epitopes in that the differentiation of peptides is based on their primary structure, which cannot be taken into account when using methods based on the use of physico-chemical characteristics of amino acids. Computer modeling of protein processing in immunoproteosomes can be a useful step in vaccine design, allowing us to anticipate the likelihood of the immune epitope being preserved for presentation to T cells. The problems in the search for vaccines are analyzed and the possibility of creating a universal vaccine against different types of cancer based on common antigens is critically evaluated, since it is impossible to present a variety of mosaics of mutational changes in each patient in one vaccine and synthesize, for example, mRNA as the most acceptable form of vaccine for the design of a universal vaccine without violating the limitations in its syntax. The prospects and problems of using therapeutic nucleic acids (small interfering RNAs, microRNAs, antisense oligonucleotides, mRNAs, and aptomers of the CRISPR-Cas9 gene editing system) against cancer, which expand the possibilities of chemotherapy and vaccinology, are evaluated.
Aim. To study the taxonomic composition of bacteria present in the leaflets of bioprosthetic heart valves (BHVs) explanted due to structural valve degeneration (SVD). Materials and methods. Eleven BHVs removed from a matched number of recipients undergoing repeat mitral valve replacement were studied. Gram staining of histological sections was used to visualize bacteria in the BHV leaflets. The nature of inflammatory infiltration in the valves was assessed by immunohistochemistry using the NovoLink Polymer DS reagent kit and antibodies to macrophage and neutrophil markers (CD68 and neutrophil myeloperoxidase, respectively). The taxonomic composition of the microbiota in the explanted BHVs was studied using 16S rRNA metabarcoding. Statistical processing of the results was performed in the GraphPad Prism 8 program; quantitative indicators were recorded as medians, percentiles, minimum and maximum values (Me [Q1–Q3; min–max]). Results. The average lifespan of the studied BHVs was 160 [89–184; 63–221] months. Macroscopic analysis confirmed the presence of changes typical for SVD (ruptures and calcium deposits) in their leaflets with the absence of vegetations typical for prosthetic valve endocarditis (PE). A sharp predominance of macrophages and the presence of single neutrophils within the inflammatory cellular infiltrates also corresponded to the diagnosis of SVD, but not PE. Bacterial colonies located near fibrin deposits were noted in all valves. Metagenomic sequencing revealed DNA of bacteria from 106 genera, with an average of 37 [35–40; 31–44] taxa per BHV. The main contaminants of BHVs, accounting for more than 1
Background: Pseudomonas aeruginosa is a significant pathogen in nosocomial infections due to its adaptability and intrinsic resistance mechanisms. This study investigates the antibiotic and biocide susceptibility of P. aeruginosa isolates from clinical and hospital environments, emphasizing efflux pumpmediated resistance. Materials and methods: From November 2023 to April 2024 a total of 200 samples were collected, comprising 100 clinical and 100 environmental isolates from five hospitals in Hamadan, Iran. Antibiotic susceptibility was determined according to CLSI guidelines, and biocide susceptibility was tested against agents such as chlorhexidine and triclosan. Molecular analysis, including PCR and gene expression profiling, was performed to identify efflux pump-related resistance genes. Results: Among clinical isolates, 22
The Aim of the Review is to describe the structure and peculiarities of modern primate biobanks, their role in international scientific networks, as well as specialized genomic resources for the studies on hominids and other models. The review presents modern methods for authentication and genetic passportization of biological samples, such as microsatellite and SNP analysis that provide a high accuracy of identification of individuals and quality control of materials. A special attention is paid to the importance of standardization of processes and international collaboration to improve the efficiency of studies and preserve the genetic diversity. Conclusions. The authors conclude that the integration of genetic information into digital ecosystems of primate biobank leads to a transition from traditional collections to intelligent platforms that use the advanced technologies of analysis and modeling, which opens up new prospects for the studies and personalized medicine.
Abstract—Objective. New advances in genomic editing field have led to the creation of DNA base editors. Such a tool allows to make precise changes to the genome without double-stranded DNA breaks, which reduces its mutagenicity. As a result, DNA base editors are becoming a popular tool for gene therapy and transgenesis of cell lines and laboratory animals. Certainly, there is a need not only to evaluate the effectiveness of editing, but also to create new forms of DNA base editors through evolution. The purpose of our work is to create system to evaluate the effectiveness of DNA base editors and their evolution to obtain new forms. Materials and methods. Classical methods of genetic engineering were used in the work. The proportion of cells with the target effect was assessed by flow cytometry. Results. It is shown that the created systems simulate transgene expression depending on the state of its start-codons. It was revealed that editing of the first start-codon plays a key role in the initiation of translation or its inhibition. Conclusions. Based on the developed systems, it is possible to evaluate the effectiveness of editing the first start-codon of the HIV-1 gag gene and the evolution of DNA base editors to obtain new forms.
The aim of the research was to study the effect of volatile organic compounds (VOCs) of various types, secreted by microorganisms (ketones, alcohols, terpenes, dimethyl disulfide (DMDS)), on the planktonic growth and formation of the Gram-negative marine bacterium Vibrio harveyi BB120 biofilms. This pathogen bacterial species causes infectious diseases of various marine organisms (vertebrates and invertebrates), which hinders the development of marine aquaculture. Materials and methods. The cells were grown on 96-well polystyrene plates with light shaking. The planktonic growth was determined by optical density. The level of formed biofilm was determined by staining them with crystal violet with subsequent ethanol extraction. The level of biofilm formation was estimated by the color intensity of the solution. Results. It was demonstrated that the effect of all studied VOCs led to a decrease of the planktonic growth of V. harveyi BB120. (–)-Limonene, β-ionone, and (+)-α-pinene had the strongest effect on bacteria; 2-phenylethanol had a slightly weaker effect. The level of biofilms (as a percentage of the control without VOC) in all cases was higher when exposed to the indicated VOC than the level of planktonic growth of V. harveyi BB120, which indicates a higher resistance of the cells in biofilms to VOC. The patterns of the effect of various VOCs on the biofilm formation in the studied VOC ranges were different. With an increase in the amount of the added 2-pentanone and DMDS, an increase in biofilm formation was observed; the addition of (–)-limonene, 2-phenylethanol, isoamyl alcohol, and (+)-α-pinene to the culture led to a decrease in the level of biofilms. Conclusions. The inhibitory effect of VOCs with different structures (2-pentanone, β-ionone, isoamyl alcohol, 2‑phenylethanol, (–)-limonene, (+)-α-pinene, dimethyl disulfide) on the growth of V. harveyi BB120 was for the first time demonstrated. These data are of interest for the control of infections caused by V. harveyi and other pathogenic representatives of the genus Vibrio.
The aim of the study was to analyze biotechnological approaches to the construction of an internal control sample (ICS) in the manufacture of gene diagnostic preparations and the development of such an ICS for PCR test systems produced by the Microbe Russian Anti-Plague Institute. Materials and methods. To create an artificial nucleotide sequence that no known organism has, the online resource Random DNA Sequence Generator was used. Specific primers for generation of artificial nucleotide sequences were selected using DNA-Works software (v3.2.4.). Oligonucleotides were synthesized using the standard solid-phase amidophosphite method on an ASM-800 automatic DNA synthesizer. Cloning of the amplification products used as the ICS was performed in the pAL2-T vector. Bacteria culturing and bacterial clone selection were carried out on Luria-Bertani (LB) agar medium containing 50 μg/mL of ampicillin as a selective factor. Results. The paper presents data on biotechnological approaches to constructing ICSs. In the first case, a 174-bp region of the green fluorescent protein gene sGFP-206 (gfp) of the jellyfish Aequorea victoria was selected to create an exogenous ICS, since the presence of this sequence in the studied samples was virtually excluded. In the second case, an artificial nucleotide sequence was created that no known organism possesses. When developing a diagnostic set of reagents for detecting V. cholerae strain DNA in the studied clinical samples using PCR with hybridization-fluorescence registration of results, one of the tasks was to construct an endogenous internal control sample. It was proposed to use human DNA genes as a DNA target for the ICS. Studies were conducted to assess the efficiency of amplification of ICS fragments with primer annealing temperatures of 49, 58, and 60°C according to the working protocols of the produced test systems and the absence of a negative impact on the efficiency of the studied gene-fragment amplification reaction. Conclusions. The employed approaches allowed three variants of ISOs to be created for implementation of control with the help of RT-PCR of produced sets of reagents to identify the DNA of pathogens of especially dangerous infectious diseases, such as cholera, plague, anthrax, brucellosis, and tularemia with hybridization-fluorescence registration of results.
The aim of the work. Design and investigation the properties of a prototype for a single intranasal vaccine based on a recombinant Sendai virus Moscow strain expressing as an immunogen the S protein of the JN.1 variant, and an assessment of its cross-activity against a range of other SARS-CoV-2 variants. Materials and methods. A recombinant Sendai virus with transgene S(JN.1) insertion between the P and M genes was obtained by genetic engineering and RT-PCR. Expression of the transgene S(JN.1) was analyzed by immunoblotting. The immunogenicity of the vaccine construct was evaluated by ELISA and virus-neutralization assays in BALB/c mice. The protection was assessed in K18-hACE2 mice by the level of reduced replication (quantitative RT-PCR) and the decrease in the infection titer (on Vero E6 cells) of SARS-CoV-2 in the tissues of the nasal cavity and lungs of vaccinated animals. Results. Based on the Moscow strain of the Sendai virus, the vaccine construct Sen-S-JN.1(M) has been developed, which expresses the S protein of the circulating variant JN.1 of SARS-CoV-2. It has been shown that S protein is effectively exposed on Sen-S-JN.1(M) virions and induces the formation of a mucosal and systemic humoral immune response against SARS-CoV-2 variant JN.1 during a single intranasal vaccination of BALB/c mice. Analysis of the cross-neutralizing activity revealed a significant decrease in antibody titers against variants Delta, BA.1, XBB.1.5, and EG.5.1 while maintaining a high level of neutralization against XBB.1.16 and BA.5.2 variants. The K18-hACE2 mice vaccinated with Sen-S-JN.1(M) were well protected from SARS-CoV-2 (JN.1) infection due to a significant (more than 106 fold) reduction in viral replicative activity. None of the lung and turbinate samples from the vaccinated mice contained detectable levels of infectious SARS-CoV-2, which indicates that the infection had stopped. Conclusions. The recombinant virus Sen-S-JN.1(M) is a promising vaccine construct and can provide cross-protection against circulating and evolutionarily similar variants of the SARS-CoV-2 Omicron lineage.
The problem of predicting a culprit of the future influenza pandemic is analyzed in connection with the emerged epizootic of cows caused by the avian influenza H5N1 strain. The emerged epizootic in cows is considered as acquisition of a new host by the H5N1 virus. The reproductive cycle of the H5N1 virus is adapted to a high temperature. In cows, the body temperature varies and is closer to the body temperature in birds than in human. The H5N1 virus nucleoprotein is distinguished by a high content of arginine and lysine, which causes the optimum of viral replication and transcription at elevated host body temperature. In this aspect, the acquisition of cows (but not human) as a host by the H5N1 virus is more optimal. Another peculiarity of the H5N1 virus, which excludes the possibilities of its transmission into the human population, is associated with the peculiarities of its internal proteins (particularly, with a biomarker of influenza virus pandemicity). The invariance matrices of all primary structures of internal proteins of the H5N1 virus differ significantly from those in the strains of influenza pandemics in 1918, 1957, 1968, and 2009, which also does not support the prediction about the H5N1 virus as a herald of a future influenza pandemic. Conclusions. Based on the history of the emergence of last four influenza pandemics and comparison of biological properties and molecular characteristics of hemagglutinins of influenza viruses of the H1N1 and H3N2 subtypes, the H1N1 virus subtype is assumed to be the most likely causative agent of a future influenza pandemic.
Objective—to investigate the possibility Aim was to study a possibility of encapsulation of hydrophilic B/C and P forms of riboflavin into calcium alginate particles, to study riboflavin release from the particles and its antibacterial properties. Materials and methods. Alginate particles were obtained by cross-linking of sodium alginate with calcium ions and loaded in situ with B/C and P types of riboflavin. The strains of Pseudomonas aeruginosa bacteria were used to evaluate antibacterial activity. Results. Two polymorphic modifications and salt form of riboflavin (types A, B/C, and P) were successfully encapsulated into calcium alginate particles of about 600 μm in size. Using the methods of optical and electron microscopy, it was demonstrated that types A and B/C retain the shape of crystals and crystalline intergrowths, while type P riboflavin is uniformly distributed in the gel matrix. X-ray phase analysis confirmed the preservation of the crystalline form of type A riboflavin, but revealed that the crystalline aggregates of type B/C become amorphous during encapsulation. It was demonstrated that alginate particles containing type B/C riboflavin are characterized by a prolonged release of the active substance into deionized water, and the equilibrium concentration for type P is already reached within 30 min. It was established that the particles loaded with types B/C and P exhibit a pronounced antibacterial activity against Gram-negative bacteria. Conclusions. The encapsulation of types B/C and P riboflavin into alginate particles allows us to preserve the antibacterial activity of the substance and provide its controlled release.
Study objective. The aim was to investigate the effect of perennial agrophytocenoses based on variable alfalfa (Medicago sativa var. varia), grown either as a monoculture or in mixture with grasses, on soil microbial diversity under different mowing regimes using high-throughput profiling of soil microbial communities based on the 16S rRNA gene. Materials and methods. The study was conducted at the Field Experimental Station of the Russian State Agrarian University—Moscow Timiryazev Agricultural Academy in a field experiment established in 1996. DNA was isolated from soil samples collected from the upper organomineral horizon using the Qiagen PowerSoil Pro DNA Kit (Qiagen, Germany) according to the manufacturer’s standard protocol on a QiaCube automated workstation (Qiagen, Germany). Amplification was performed using primers whose target regions corresponded to the 515F/Pro-mod-805R primers, while the technical sequences included a heterogeneity spacer, a 6-nucleotide index, and a standard Illumina adapter. Primary filtering of low-quality reads was carried out using the reformat.sh software from the BBTools package. Results. An increased abundance of nitrogen-fixing microorganisms of the genus Bradyrhizobium was detected in experimental plots sown with alfalfa or alfalfa–grass mixtures compared to arable land. Two-cut mowing was associated with greater variability in alpha-diversity metrics compared to three-cut mowing. In addition, a two-cut mowing regime was shown to be more favorable for the accumulation of fixed nitrogen in the soil compared to three-cut mowing, due to more efficient development of a branched root system and, consequently, increased intensity of metabolic fluxes in the rhizosphere. Conclusions. The results demonstrate the possibility of maintaining agrocenosis productivity by managing the composition of soil microbiota through optimization of the botanical composition of grass stands and agronomic practices.
Heterochromatic position effect variegation (PEV) of the gene comprises euchromatic gene inhibition upon its transition in the area of heterochromatin either at the same chromosome, for example, in case of inversions (cis-acting PEV), or at the contact of the euchromatic gene with the heterochromatin associated with the allele of the same gene in the homologous chromosome in the three-dimensional nuclear volume (trans-acting PEV). The reverse PEV consists in heterochromatic gene inhibition in case it is placed in euchromatic environment. Most PEV data were obtained using genetic system of Drosophila melanogaster that has four chromosomes combined in the chromocenter. Heterochromatic cis-acting PEV often takes place in case of invertions such as In(2)A4; In(1)wm4. Molecular mechanisms of cis-acting PEV include expression level changes of several genes due to the changes in the quantities of specific histone modifications, heterochromatin proteins (HP1) and specific small RNA including piRNAs. In case of cis-acting PEV the distribution of heterochromatic modifications (H3K9me2/3) and main heterochromatic protein (heterochromatin protein HP1a) from the heterochromatin to the euchromatin area is well studied and is associated with the expression inhibition of several genes. Heterochromatic trans-acting PEV has been thoroughly investigated only in a few cases including the invertion In(2)A4 and satellite DNA fragment insertion in brown gene (bwD). In both cases genomic rearrangements took place at the second chromosome of Drosophila melanogaster. Molecular mechanisms of trans-acting PEV are less studied than those of cis-acting PEV. It was shown that Su(Var)2-HP2, SAYP, SETDB1 participate in trans-acting PEV in case of the inversion In(2)A4. Perspective research in the field of cis- and trans-acting PEV includes the study of the role of prod and D1 mutations that influence the integrity of Drosophila melanogaster chromocenters.
Aim. The current study aims to investigate changes in the expression of proprotein convertases (PCs) genes during the development of lung tumors. PCs are a family of highly specific subtilisin-like serine endopeptidases of mammals that process precursors of various proteins and peptides. Nine genes encoding PCs have been identified in the human genome that are essential for normal body functioning. Additionally, PCs can activate proteins involved in carcinogenesis, as well as the expression levels of their genes were shown to correlate with tumor aggressiveness and patient survival. We previously evaluated the expression of all nine PC genes using quantitative PCR on paired samples of lung tumor and adjacent normal tissue. For the first time, we identified four distinct patterns of PCs gene expression change in tumor tissue, which we have called scenarios. For three of them, covering more than two thirds of the samples, a dominant change in the expression of one PC gene in the tumor tissue was shown. These results may indicate the existence of a limited number of possible options for changes in PCs gene expression during the malignant transformation of lung cells. However, these results need to be confirmed using expanded cohort of tumor samples. Materials and methods. To confirm our previous findings, we analyzed the expression of PCs genes using modern methods of mathematical statistics and data from three previously published studies, which evaluated gene expression through high-throughput RNA sequencing in paired tumor and normal tissue samples from 194 patients with non-small cell lung cancer. Results. Our meta-analysis confirmed that the changes in PCs gene expression in lung tumor tissue compared to adjacent normal tissue follow a limited set of possible scenarios, each having a unique profile of PCs gene expression. Conclusions. The reasons for implementing each scenario may be linked to the origin of tumors, their mutation status, characteristics of the tumor microenvironment, and other factors. Correspondingly, these scenarios may correlate, for example, with tumor aggressiveness and resistance to therapy, and therefore may potentially be used to choose the treatment approach and/or to predict the course of the disease. However, this issue requires further research.
