Aim: to examine the characteristics of mixed (metabolic + alcoholic) fatty liver disease (FLD) in relation to Helicobacter pylori infection Patients and Methods: the study included 30 men with signs of hepatic steatosis detected by ultrasound. The patients underwent a com- prehensive clinical and laboratory examination, which included a detailed history of their drug use, an interview about their gastrointestinal symptoms, their alcohol consumption and smoking habits, a complete blood count, and blood biochemistry. H. pylori infection was diagnosed by one-step immunochromatography to detect specific H. pylori antigens in feces. The criteria of the All-Russian Scientific Society of Cardi- ologists were applied to diagnose metabolic syndrome (MS). Indirect liver elastometry was performed using the FibroScan® 502 (Echosens, France) to assess the severity of liver fibrosis (in kPa) with rating of fibrosis stage according to the METAVIR score (F0–F4). Results: MS was identified in 96.7% of patients. Systematic alcohol consumption, defined as consumption of alcohol at least once a week, was common (87%) in these patients. The mean single dose was 103.1±62.86 g, and the mean weekly dose was 211.0±133.8 g (pure ethanol). H. pylori infection was detected in 56.7%. In 18 (60%) patients, liver elastography showed no fibrosis (F0). Stages F1-3 were revealed in 40% of patients, with F1 observed in 26.7%, F2 in 6.7%, and F3 in 6.6%. No significant differences in the parameters were identified based on H. pylori infection status Conclusion: all patients exhibited signs of FLD of mixed origin, associated with both metabolic disorders and systematic alcohol consumption. A greater proportion of patients (56.7%) were found to be infected with H. pylori. The analysis of MS manifestations, alcohol consumption style, smoking, liver tests, liver elasticity, and fibrosis stage revealed no significant differences depending on H. pylori infection. This may be due to the relatively small sample size in this pilot study. KEYWORDS: fatty liver disease, nonalcoholic fatty liver disease, metabolic syndrome, Helicobacter pylori, fibrosis, insulin resistance. FOR CITATION: Belkovets A.V., Kruchinina M.V., Galanova A.V., Shcherbakova L.V. Helicobacter pylori infection and fatty liver disease (results of a pilot study). Russian Medical Inquiry. 2024;8(5):253–259 (in Russ.). DOI: 10.32364/2587-6821-2024-8-5-2.
Introduction. Fatty liver disease is the largest contributor to the burden of chronic liver disease worldwide. Current approaches do not allow sufficient differentiation between alcoholic and non-alcoholic etiology of the process.Aim. Create diagnostic panels including electrical and viscoelastic parameters of erythrocytes to differentiate fatty liver disease of alcoholic and non-alcoholic genesis.Materials and methods. The study included 38 men (47.5 ± 2.9 years) with NAFLD; 31 men with alcoholic fatty liver disease (AFLD) (45.1 ± 3.1 years) according to ultrasound of the abdominal organs, the degree of fibrosis did not exceed F1 (FibroScan® 502). Electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis using an electro-optical cell detection system. To determine the parameters of erythrocytes – biomarkers for distinguishing between AFLD and NAFLD, a system of machine learning methods – Random Forest was used.Results. Electrical, viscoelastic parameters of erythrocytes, which are biomarkers for distinguishing between AFLD and NAFLD, were established: cell membrane capacity (p = 1.21E-11), the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz (p = 2.38E-08), cell polarizability at a frequency of 106 Hz (p = 9.38E-08), the speed of erythrocyte movement to the electrodes (p = 4.32E-06), the magnitude of the dipole moment (p = 1.66E-05), relative polarizability (p = 2.35E-05), the index of erythrocyte destruction at a frequency of 5 x 105 Hz (p = 0.016), the position of the crossover frequency (p = 2.13E- 06). The diagnostic model, including five parameters – the position of the crossover frequency, cell polarizability at a frequency of 106 Hz, cell electrical conductivity, membrane capacity, the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz, provided the highest diagnostic accuracy with an AUC of 0.975, a sensitivity of 96.3%, and a specificity of 91.8% in differentiating between AFLD and NAFLD.Conclusion. Thus, systematic exposure to alcohol modifies the structure of erythrocyte membranes, leading to a decrease in the surface charge, the barrier function of membranes, reducing the resistance of cells, their ability to deform, which determines the key role of the identified electrical, viscoelastic parameters of erythrocytes in differentiating between AFLD and NAFLD.
Early diagnosis of autoimmune gastritis (AIG) is quite difficult in a physician’s daily practice. Since the disease is asymptomatic for a long time, it is often diagnosed already with severe atrophy with the loss of a large number of gastric glands and potentially significant pernicious anemia, and sometimes with the onset of cancer. Morphological and endoscopic changes do not occur immediately and are not specific in patients with AIG. In this case, non-invasive diagnostics play a key role. The diagnostics of AIG are often done in patients with vitamin B12 and iron deficiency. However, the development of these deficiencies can take a long time. The non-invasive technique with the determination of such biomarkers as pepsinogen I, II (PGI, PG II), their ratio, gastrin-17, as well as Helicobacter pylori (H. pylori) infection, including a cytotoxic (CagA +) strain, is used to exclude preclinical stages of AIG. The titer determination of anti-parietal cell antibodies and the anti-intrinsic factor antibodies allows identifying the immune nature of gastritis. But recent studies show that these markers can be negative in some patients. This article actualizes the problem of early diagnosis of AIG and demonstrates the importance of practical application of currently existing non-invasive methods for the diagnosis of stomach diseases.
Aim of the study was to investigate the features of the fatty acid (FA) profile of erythrocyte membranes of patients with fatty liver disease (FLD) of mixed genesis (metabolic + alcoholic) from the point of view of atherogenic changes.Material and methods. 31 men (50.6 ± 9.9 years old) with FLD of mixed genesis, the degree of liver fibrosis corresponded to 0-1 (FibroScan ® 502 Echosens, France), and 28 persons of the comparison group, comparable in age, were examined. The study of the composition of FAs of erythrocyte membranes was carried out using gas chromatography/mass spectrometry – a system based on three quadrupoles Agilent 7000B (USA).Results. Patients with FLD of mixed genesis had higher level of palmitoleic (p = 0.03), pentadecanoic (p = 0.05), omega-6 to omega-3 polyunsaturated fatter acids (PUFA) ratio (p = 0.03) and, conversely, lower level of docosahexaenoic (p = 0.0002), total content of eicosapentaenoic and docosahexaenoic FA (p = 0.0007), of all omega-3 PUFA (p = 0.001) in the membranes of erythrocytes compared to healthy persons. There are trends towards a decrease in the content of omega-3 eicosapentaenoic acid and an increase in the ratio of SFA/PUFA in patients with fibroids of mixed genesis in contrast to healthy individuals. The level of individual FA provided high diagnostic accuracy in differentiating patients with FLD of mixed genesis from healthy individuals: palmitoleic (9-C16:1) (area under ROC (AUC) 0.702, sensitivity 66.7 %, specificity 69.6 %), docosahexaenoic (C22:6n-3) (AUC 0.795, sensitivity 77.3 %, specificity 78.3 %), as well as the total content of eicosapentaenoic and docosegexaenoic FA (C20:5n-3 + C22:6n-3) (AUC 0.777, sensitivity 70.1 %, specificity 82.6 %).Conclusions. The revealed features of the profile of erythrocyte membrane FA in FLD of mixed genesis – increase of saturated, monounsaturated, omega-6 PUFA content and reduce of omega-3 PUFA concentration are atherogenic. The continuation of research in terms of the use of FAs as biomarkers of this pathology and targets for therapeutic effects should be considered promising.
Aim: to study the possibilities of using electrical and viscoelastic parameters of erythrocytes to differentiate steatohepatitis from liver steatosis. Patients and Methods: 84 men (48.9±2.5 years) with fatty liver disease diagnosed by abdominal ultrasound were examined. Liver fibrosis severity, which did not exceed grade 1, was determined by indirect elastometry on the FibroScan® 502 Echosens device (France), with confirmation using the FibroTest–ActiTest test system (BioPredictive, France). Patients were divided into 2 groups according to the severity of hepatic necroinflammatory activity, assessed using the same test system. Group 1 (n=44) included patients with hepatic steatosis with minimal histologic disease activity (A 0–1); group 2 (n=40) included patients with steatohepatitis with significant necro-inflammatory activity (A 2–3). The electrical and viscoelastic parameters of erythrocytes were determined by dielectrophoresis at 4 frequencies of an inhomogeneous alternating electric field. Results and Discussion: the most significant electrical and viscoelastic indicators allowing to differentiate steatohepatitis from fatty liver disease were reduced values of strain amplitude at a frequency of 1 MHz (p=0.0003), dipole moment (p=0.009), capacity (p=0.014) and cell polarizability at a frequency of 1 MHz (p=0.03) and more high summarized viscosity (p=0.006), rigidity (p=0.005) and electrical conductivity (p=0.008). Diagnostic panel, including a set of electrical and viscoelastic parameters of erythrocytes, for the differentiation of steatohepatitis from steatosis demonstrated the following: AUC 0.904, sensitivity 0.9, specificity 0.83. Correlations of erythrocyte parameters with indicators of cytolysis syndrome (transaminase activity, serum iron levels, direct bilirubin) and serum inflammatory markers (fibrinogen, C-reactive protein, ferritin) were established. Conclusion: the electrical and viscoelastic parameters of erythrocytes studied using the dielectrophoresis should be considered as a new promising method in determining the severity of fatty liver disease. KEYWORDS: fatty liver disease, steatohepatitis, steatosis, electrical and viscoelastic parameters, erythrocytes, dielectrophoresis, diagnostic model. FOR CITATION: Kruchinina M.V., Parulikova M.V., Belkovets A.V., Gromov A.A. Possibilities of using electrical and viscoelastic parameters of erythrocytes for the diagnosis of steatohepatitis in patients with fatty liver disease. Russian Medical Inquiry. 2023;7(5):249–257 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-2.
Patients with autoimmune gastritis (AIG) often have anemia of various origins. Hematological disorders usually portend severe atrophy, and in many cases, are the only indicators of the disease. Aim of the study was to investigate the electrical and viscoelastic parameters of erythrocytes in patients with AIG for their possible use in diagnostics. Material and methods. 73 patients with AIG (mean age 55.3 ± 12.54 years) and 38 people of the control group were examined. Electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis. Results. Statistically significant decrease in the average cell diameter, the proportion of discocyties cells and an increase in the proportion of spherocytes, deformed forms were found in the group of patients with AIG in combination with Helicobaсter рylori (H. pylori, H.p.) infection compared with healthy individuals. Patients with AIG had significantly lower levels of amplitude of deformation, membrane capacity, dipole moment, speed of cell movement to the electrodes, polarizability at high frequencies of the electric field (106, 0.5×106 Hz), relative polarizability, and, conversely, higher values of membrane conductivity, aggregation, destruction indexes, summarized viscosity, rigidity, than those in the comparison group. Between groups of patients with and without H. pylori infection, differences were found in indicators reflecting the surface charge of erythrocytes – the speed of movement to the electrodes (p = 0.019), the dipole moment (p < 0.001) and the state of the membranes – its capacity (p = 0.004). The diagnostic model, which includes three parameters of erythrocytes – the dipole moment, the speed of movement to the electrodes, the capacity of the cell membrane, provided high diagnostic accuracy of distinguishing AIG H.p. (+) and H.p. (–) – area under ROC curve AUC 0.925, sensitivity 92.4 %, specificity 89.7 %. Conclusions: Electrical and viscoelastic parameters of erythrocytes are promising in the diagnosis of AIG, including on the background of H. pylori infection.
The article presents a clinical case of a 38-year-old patient with revealed polyps of the stomach body and iron deficiency anemia on the background of chronic atrophic gastritis. On the example of this observation, variants of the course were demonstrated, including endoscopic and histological manifestations of autoimmune (atrophic corpus) gastritis (AIG). In parallel, the issues of diagnosis and management of patients with the most common polyps in the stomach are discussed. The problem of timely diagnosis of AIG and the advantages of non-invasive methods for assessing the functional state of the stomach is also being actualized.
Background : some researchers have demonstrated a link between the genetic polymorphism of certain pro-infl ammatory cytokines (IL-1β, IL-6) and the risk of developing precancerous diseases of the stomach and gastric cancer (GC). Aim : to study the genotypes and alleles frequency of polymorphisms of –511C/T (rs16944) of the IL1B gene and 174G/C (rs1800795) of the IL6 gene in patients with serologically detected atrophic gastritis (AG) — the main precancerous lesions of the stomach. Materials and methods . the study included 55 people (45 females and10 males) with an average age of 58.2 ± 11.5 years with signs of obvious or possible atrophy of diff erent parts of the gastric mucosa revealed by enzyme-linked immunosorbent assay (ELISA) with determination of pepsinogen levels I (PGI), PGII, the PGI / PGII ratio, gastrin-17 and IgG antibodies to H. pylori using the “GastroPanel” diagnostic kit (Biohit Plc, Helsinski, Finland). DNA was isolated from venous blood using the phenol-chloroform extraction method. DNA samples were genotyped according to published methods. Results : in patients with severe AG (PGI level less than 30 μg/l), the combined variant with the rare T allele (T/T + C/T) was detected signifi cantly more often (68.8%) than the common homozygous C/C variant (31, 3%, p = 0.004). In individuals with a low PGI/PGII ratio (less than 3), which is also evidence of fundamental atrophy, the homozygous T/T variant was more common (29.6%) than the C/C genotype (7.4%, p = 0.04) The average PGI values were signifi cantly lower with the C/C genotype of the IL-6 gene compared with the heterozygous C/G variant (p = 0.03), however, in patients with morphologically confi rmed atrophy, the combined variant with the rare G allele (G/G + C/G) of the IL6 gene was more common than the homozygous C/C variant (71.4% versus 28.6%, p = 001). Conclusions : in patients with signs of corpus atrophy (low PGI, PGI PGII ratios), the homozygous variant with a rare T allele, which is associated with increased IL-1β production and the development of a hypoacid state, was 4 times more likely than the homozygous C/C variant (p = 0.04). The results obtained suggest a possible association of IL1B polymorphism (carriage of a rare T allele) with the formation of a cancer phenotype of gastritis. The contribution of IL6 polymorphism requires further refi nement.
В статье представлен клинический случай пациента 63 лет с анемией на фоне хронического атрофического гастрита и неэффективностью лечения препаратами железа. На примере данного наблюдения проанализированы ошибки, возникающие при диагностике и ведении пациентов с аутоиммунным (атрофическим фундальным) гастритом (АИГ). Параллельно обсуждаются вопросы патогенеза АИГ, связи с Helicobacter рylori (H. pyloi) инфекцией. Актуализируется проблема своевременной диагностики АИГ и преимуществ неинвазивных методик оценки функционального состояния желудка.
Background. Atrophic gastritis (AG), being the basic premalignant condition for the stomach cancer (SC), is commonly diagnosed and screened for by noninvasive biomarkers (pepsinogens, gastrin-17), however the data on those biomarkers at SC is inconsistent. Aim of investigation. To evaluate the markers of stomach atrophy along with risk factors of SC of different localization, histological type and stage in the «case series» study. Material and methods. Original investigation was designed as «case series», that included 85 patients with SC (48 m and 37 f, mean age 61.2±13,6 years) who were consistently referred to two medical institutions. All patients underwent interviewing the questionnaire concerning smoking and alcohol consumption, presence of gastroenterological symptoms and family history. Blood serum samples were analyzed using ELISA test kits «GastroPanel» («Biohit Plc», Finland). Manufacturer recommended threshold levels were used at diagnostics of AG. Results. The diagnosis of SC of the III to IV stage was established in 67.9% of patients. The most common location of the neoplasm was the stomach body (63,5%). Helicobacter pylori (H. pylori) infection was revealed by serological method in 74.1% of cases, of which in 15.1% the attempt of eradication treatment was carried out. In 90.6% of patients the adenocarcinoma of different differentiation grade was diagnosed, low degree of differentiation was the most common (57.6%). Signet-ring cell carcinoma was diagnosed in 7.1% of patients, undifferentiated tumor - in 2.4%. Pepsinogen-I (PGI) level under 50 mcg/l was found in 43.2% of patients, indicating different degrees of fundic atrophy. Significantly lower PGI scores were detected in SC patients with histologically verified atrophy. No significant differences in biomarker levels according to tumor location, histological type of SC and tumor stage were found. Conclusions. The «case series» study demonstrated high rate of late SC diagnostics with predominance of corpus location and the most malignant types. H. pylori infection was diagnosed in serologically in the most of patients, however attempts for eradication therapy was carried out only in 15% of patients. Fundic atrophy was diagnosed by serological tests in over 40% of patients, however no association with location, stage and morphological type of the tumor was established. Blood serum samples were analyzed using ELISA test kits «GastroPanel» («Biohit Plc», Finland). Manufacturer recommended threshold levels were used at diagnostics of AG.
Background. A functionally significant TP53Arg72Pro polymorphism can contribute to the development of gastric cancer (GC). The aim: to study the associations of genotypes and alleles of the TP53Arg72Pro 4 polymorphism with GC and biomarkers of gastric ucosal atrophy in population-based prospective and case-control clinical trials among the population of Siberia. Material and methods. As a part of the epidemiological study, data of the international multicenter HAPIEE project for 2003–05, based on a population sample of residents of Novosibirsk city (serum and DNA samples) and data of the population-based registry of GC (2012) were compared. Gastric cancer patients were matched by age and sex to HAPIEE population controls. A total of 156 serum samples (GC – 52, control – 104) and 146 DNA samples (GC – 50, control – 96) were available for prospective analysis. DNA samples from 80 gastric cancer patients (45 men and 35 women, mean age 61.0 ± 13.4 years) and from 87 age-and sex-matched controls were analyzed. DNA samples from venous blood were genotyped according to standard methods. Serum samples were tested using diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratio, gastrin-17 and IgG antibodies to H. pylori. Results. No differences in genotype and allele frequencies of the TP53 gene between the case group and the control group were found. A decreased frequency of the Pro allele in female gastric cancer patients compared with controls indicated that the Pro allele is protective against the development of gastric cancer, but this effect was not observed in male patients. No associations of TP53 genotypes with the risk of diffuse or intestinal gastric cancer, as well as with the age and sex of patients were found. A high frequency of genotypes with the Pro allele in patients with stage III–IV gastric cancer indicated the relationship between Arg/Pro TR53 and tumor progression, in particular, the contribution of the minor Pro allele to the unfavorable prognosis. A prospective study showed high risk of reducing the level of pepsinogen for assessing predisposition to gastric cancer. Conclusion. Two case-control studies (population and clinical) conducted in the Western Siberia found no relationship between the TP53Arg72Pro polymorphism and the risk of gastric cancer. However, the TP53 genotype with a rare Pro allele was associated with atrophic gastritis and severity of gastric cancer.
Background. A functionally significant TP53Arg72Pro polymorphism can contribute to the development of gastric cancer (GC).The aim: to study the associations of genotypes and alleles of the TP53Arg72Pro 4 polymorphism with GC and biomarkers of gastric ucosal atrophy in population-based prospective and case-control clinical trials among the population of Siberia.Material and methods. As a part of the epidemiological study, data of the international multicenter HAPIEE project for 2003–05, based on a population sample of residents of Novosibirsk city (serum and DNA samples) and data of the population-based registry of GC (2012) were compared. Gastric cancer patients were matched by age and sex to HAPIEE population controls. A total of 156 serum samples (GC – 52, control – 104) and 146 DNA samples (GC – 50, control – 96) were available for prospective analysis. DNA samples from 80 gastric cancer patients (45 men and 35 women, mean age 61.0 ± 13.4 years) and from 87 age-and sex-matched controls were analyzed. DNA samples from venous blood were genotyped according to standard methods. Serum samples were tested using diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratio, gastrin-17 and IgG antibodies to H. pylori.Results. No differences in genotype and allele frequencies of the TP53 gene between the case group and the control group were found. A decreased frequency of the Pro allele in female gastric cancer patients compared with controls indicated that the Pro allele is protective against the development of gastric cancer, but this effect was not observed in male patients. No associations of TP53 genotypes with the risk of diffuse or intestinal gastric cancer, as well as with the age and sex of patients were found. A high frequency of genotypes with the Pro allele in patients with stage III–IV gastric cancer indicated the relationship between Arg/Pro TR53 and tumor progression, in particular, the contribution of the minor Pro allele to the unfavorable prognosis. A prospective study showed high risk of reducing the level of pepsinogen for assessing predisposition to gastric cancer.Conclusion. Two case-control studies (population and clinical) conducted in the Western Siberia found no relationship between the TP53Arg72Pro polymorphism and the risk of gastric cancer. However, the TP53 genotype with a rare Pro allele was associated with atrophic gastritis and severity of gastric cancer.
Background: Genetic polymorphism of some inflammatory cytokines is associated with the risk of developing specific, H. pylori-associated diseases, including gastric cancer (GC). Aim: To study the genotypes and alleles frequencies of polymorphism 174G / C (rs1800795) of the IL6 gene and polymorphism -511C / T (rs16944) of the IL1B gene, as well as their association with biomarkers of atrophy in patients with GC in the clinical «case-control» study. Materials and methods: 80 patients with GC (45 mails and 35 females with an average age of 61.0 ± 13.4 years) from two medical centers were studied. In the control, DNA samples from 87 subjects were matched by sex and age from the base of the multicenter cohort study HAPIEE. DNA was isolated from venous blood using phenol-chloroform extraction. DNA samples were genotyped according to published methods. Serum samples were tested using a diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratios, gastrin-17 and IgG antibodies to H. pylori. Results: In the general group, association of polymorphisms of 174 G/C of the IL6 gene and the -511C/T gene of the IL1B gene with the GC was not found. However, in women, the frequency of the G/G genotype of the IL6 gene was 2 times higher in the group with G/C than in the control (p=0.03). In patients with corpus atrophy, the G/G genotype was revealed twice as often as homozygous C/C variant of the IL6 gene (p=0.002). In patients with GC, the genotype with a rare T allele (C/T + T/T) of the IL1B gene was significantly more frequent than the common homozygous C/C variant (p=0.03). The rare homozygous T/T genotype was significantly less frequent in patients with GC and no signs of corpus atrophy (PGI >30 μg/l): 11.3% vs 47.2% (C/T genotype) and vs 41.5% (genotype C/C) (p <0.001). Conclusions: The received data allow assuming the possible connection of studied polymorphisms with the formation of a cancer phenotype of the gastritis, which requires further study of their significance (weight) in the GC riskometry.
Aim of investigation. To study antisecretory activity of the first dose of esomeprazole (20 or 40 mg) (Emanera®, «KRKA», Slovenia) by long-term intragastric pH monitoring. Material and methods. Long-term intragastric pH monitoring was carried out in 20 patients with acidrelated diseases by «Gastroskan-24» device («IstokSistema», Fryazino, Russia). In the first 24 hours patients received no antisecretory agents, in the morning of the next day - they received esomeprazole 20 or 40 mg orally 30 min. prior to the breakfast. Median pH, both time with various pH values and area under pH distribution curve, percent of this time with values from 1,0 to 10,0 per day before and after esomeprazole administration were estimated. The respective scores were compared, using Wilcoxon criterion. Differences were considered to be significant at р
Background: atrophic gastritis (AG) associated with Helicobacter pylori (H. pylori-infection) is one of the precancerous lesions and associated with low level of serum pepsinogen I (PGI) and PGI/PGII ratio, which are also recognized like predictive markers for gastric cancer (GC) development. The aim of the study: to analyze the predictive value of biomarkers in the GC development in a prospective “case-control” study conducted in Caucasian population of Western Siberia (8 years follow-up). Material and Methods: GC cases and control were selected from population cohort of residents of Novosibirsk within the international HAPIEE project during 2003-2005 with inclusion of subjects (n=9360) of both sexes at the age of 45-69 years. Serum samples were stored at -70 0 С. GC cases received from Population Cancer Registry until 2012 were compared with the database of HAPIEE with selection of appropriate on sex and age control in the ratio 1:2. Finally, 156 serum samples (52 - the main group and 104 - control) were available for analysis, and biomarkers were measured. The following criteria for biomarkers of atrophic gastritis were used: PGI < 30 µg/l, PGII < 3 µg/l, PGI/PGII < 3, G-17 < 1 pmol/l. Results: The mean levels of PGI and PgI/PgII ratio in the GC group was lower in comparison with the control (p < 0.005 and p< 0.0001, respectively); no difference was shown in respect to the other biomarkers. The cut-off values of atrophy have appeared above the recommended parameters: for PGI-55 µg/l (р=0.0001; OR=4.1; 95 % CI 2.0-8.4) and PGI/PGII ratio-5 (р=0.0001; OR =5.8; 95 % CI 2.7-12.4). Conditional (fixed effects) logistic regression analysis with inclusion into the model sex, age of the patients, and all biomarkers of test system showed PGI/PGII ratio as the most powerful indicator in the model (OR=2.9; 95 % CI: 1.0-8.0). Conclusions: for the first time the predictive value of low indicators of PGI and PGI/PGII ratio in GC risk development in Caucasian population for 8 years follow-up was demonstrated.
Introduction. Searching for specific and sensitive molecular tumor markers is one of the important tasks of modern oncology. These markers can be used for early tumor diagnosis and prognosis as well as for prediction of therapeutic response, estimation of tumor volume or to assess disease recurrence through monitoring. Gene expression data base mining followed by experimental validation of results obtained is one of the promising approaches for searching of that kind.Objective: to identify several membrane proteins which can be used for serum diagnosis of intestinal type of gastric adenocarcinoma.Materials and methods. We used bioinformatic-driven search using Gene Ontology and The Cancer Genome Atlas (TCGA) data to identify mRNA up-regulated in gastric cancer (GC). Then, the expression levels of the mRNAs in 55 pare clinical specimens were investigated using reverse transcription polymerase chain reaction.Results. Comparative analysis of the mRNA levels in normal and tumor tissues using a new bioinformatics algorithm allowed to identify 3 high-copy transcripts (SULF1, PMEPA1 and SPARC), intracellular content of which markedly increased in GC. Expression analysis of these genes in clinical specimens showed significantly higher mRNA levels of PMEPA1 and SPARC in tumor as compared to normal gastric tissue. Interestingly more than twofold increase in expression level of these genes was observed in 75 % of intestinal-type GC. The same results were found only in 25 and 38 % of diffuse-type GC respectively.Conclusions. As a result of original bioinforamtic analysis using TCGA data base two genes (PMEPA1 and SPARC) were shown to be significantly upregulated in intestinal-type gastric adenocarcinoma. The findings show the importance of further investigation to clarify the clinical value of their expression level in stomach tumors as well as their role in carcinogenesis.
Background: Serum biomarkers of atrophic gastritis (pepsinogen I (PGI) and PGI/PGII ratio) are important for gastric cancer (GC) risk stratification. According to a number of researches IL1В gene polymorphisms are associated with risk of GC. The aim: to study the association of IL1В gene promoter polymorphism (-511C/T (rs16944) with GC in the prospective “case-control” study (8 years follow up). Materials and methods: the base of biomaterials received in 2003-2005 in population selection of residents of Novosibirsk within the international HAPIEE project (DNA samples and serums were stored at - 70 0 C) were compared with data of the population register of GC (in 2012). For each case of GC, an appropriate control case was selected at the ratio 1:2 matching the area of residence, sex and age. Finally 156 serum samples (52 - GC group and 104 - control) were available for the analysis using a panel of serum biomarkers “Gastropanel” (Biohit, Finland) and 141 DNA samples (49 - GC group and 92 - control) were genotyped according to the published method. Results: the frequency of T/T genotype of the IL1В was found significantly higher in the GC group (16.3 %) compared with the control (5.4 %) (p=0.03). The T/T genotype was associated with significantly increased risks of GC compared with the C/C genotype (OR=3.4; СI: 1.0-11.0, р=0.03). It was shown that rare T allele carriers have increased risk GC development (OR=1.69; CI: 1.01-2.81, р=0.04) in comparison with wild C allele carriers (OR=0.59; CI: 0.36-0.99, р=0.04). The mean level of PGI and PGI/II ratio in persons with T/T genotype were significantly lower in GC group (41.3 ±31.8 µg/l and 4.1±2.9 versus 131.0±57.2 µg/l and 7.0±2.8; p=0.0001 and p=0.05 respectively). Conclusion: IL1В polymorphism (rs16944) is associated with an increased risk of GC in the population of Western Siberia and can be discussed for inclusion in the GC riskometer.
BACKGROUND:Corpus atrophic gastritis (CAG) maybe the outcome of Helicobocterpylori (U pylon) - infection or autoimmune damage of the parietal system, affecting the risk of gastric cancer and requiring different approaches in the treatment and observation.AIM:To study the prevalence and peculiarity of CAG in population with, high prevalence of H.pylori infection.MATERIALS AND METHODS:Prevalence of CAG was studied in the representative group of Novosibirsk citizens (246 subjects aged 45-69,117 males and 129 females) using serology for noninvasive testing of gastritis phenotype Gastro-Panel. Pepsinogen I (Pgl) level < 30 pg/I and/or Pgl/Pgil ratio c 3.0 were interpreted as sever atrophy. In addition, a clinical group with serologically proven corpus atrophy was studied: 39 females and 8 males aged 38-79. Upper endoscopy and morpholojical examination was performed in 38 patients. As a pilot project, in 19 patients with suspicion on autoimmune gastritis (AIG) (low Pgl + high Gastrin-17) parietal cells antibodies (PCA) and vitamin B12 level were determined.CONCLUSION:In Novosibirsk population prevalence of both H.pylori infection and CAG (10.2%) is high. AIG is often associated with H.pylori infection (in 47.4% of cases); however, its role demands a further evaluation. Autoimmune phenotype of gastritis which was found using noninvasive diagnostic was confIrmed with the presence of PCA. In all cases ofAIG atrophy was confirmed morphologically with the presence of intestinal metaplasia in 52.6% and ~ysplasia in 10.5% of cases.