Gastric Cancer Precursor Lesions Research Articles

Pepsinogen I, pepsinogen II, gastrin-17, and Helicobacter pylori serological biomarkers in the diagnosis of precursor lesions of gastric cancer

IntroductionAtrophic gastritis and intestinal metaplasia are precursor lesions of gastric cancer. The aim of this study was to determine the usefulness of the biomarkers pepsinogen I(PgI), pepsinogen II (PgII), gastrin-17, and H. pylori antibodies in the identification of precursor lesions.MethodsWe studied 129 patients with gastric symptoms. The biomarker status was determined using GastroPanel by means of the ELISA-technique.ResultsBiomarkers detected atrophy in 14% of the subjects, and 49.6% had positive antibodies for H. pylori. A PgI/PgII ratio < 3 was an important risk biomarker for precursor lesions in our population (OR = 9.171, 95% CI: 1.723–48.799, p = 0.009); however, biomarkers showed low accuracy with histopathological study.ConclusionsIn the Western Mexican population, precursor lesions (AG, IM) are common in adults (45%) with dyspepsia but infrequent in children (8%). H. pylori infection was detected in 41.3% of adults and 16.0% of children. Of the studied biomarkers, a PgI/PgII ratio < 3 was an important risk factor for precursor lesions such as AG or IM in our population, with an OR of 9.171 (95% CI: 1.723–48.799, p = 0.009).

Pepsinogen I, pepsinogen II, gastrin-17, and Helicobacter pylori serological biomarkers in the diagnosis of precursor lesions of gastric cancer

IntroductionAtrophic gastritis and intestinal metaplasia are precursor lesions of gastric cancer. The aim of this study was to determine the usefulness of the biomarkers pepsinogen I(PgI), pepsinogen II (PgII), gastrin-17, and H. pylori antibodies in the identification of precursor lesions.MethodsWe studied 129 patients with gastric symptoms. The biomarker status was determined using GastroPanel by means of the ELISA-technique.ResultsBiomarkers detected atrophy in 14% of the subjects, and 49.6% had positive antibodies for H. pylori. A PgI/PgII ratio < 3 was an important risk biomarker for precursor lesions in our population (OR = 9.171, 95% CI: 1.723–48.799, p = 0.009); however, biomarkers showed low accuracy with histopathological study.ConclusionsIn the Western Mexican population, precursor lesions (AG, IM) are common in adults (45%) with dyspepsia but infrequent in children (8%). H. pylori infection was detected in 41.3% of adults and 16.0% of children. Of the studied biomarkers, a PgI/PgII ratio < 3 was an important risk factor for precursor lesions such as AG or IM in our population, with an OR of 9.171 (95% CI: 1.723–48.799, p = 0.009).

Protocolo de evaluación de las lesiones premalignas gástricas

Gastric carcinogenesis is associated with Helicobacter pylori(H. pylori) infection and occurs through histologic gastric cancer precursor lesions (GCPL). This protocol will discuss intestinal gastric cancer. It does not cover prevention of diffuse and cardia gastric cancer, neuroendocrine tumors, or hereditary syndromes. The most significant factors that cause an increased risk of gastric cancer are family history of the disease and the presence of GCPL. The two strategies evaluated to reduce the incidence and/or mortality of gastric cancer are eradication of H. pylori and monitoring and/or endoscopic treatments.

Association of endoscopic biopsy sampling methods with detection of precursor lesions of gastric cancer

The yield of various endoscopic biopsy sampling methods for detection of precursor lesions of non-cardia gastric cancer in a real-world setting remains unclear. Our objective was to evaluate the association of endoscopic biopsy sampling methods with detection of gastric intestinal metaplasia (GIM) and dysplasia (GD). We conducted a case-control study of adult patients who underwent esophagogastroduodenoscopy (EGD) with biopsy between 2010-2021 in a racially/ethnically diverse United States healthcare system. Cases were patients with histopathologic findings of GIM and/or GD. Controls were matched 1:1 by age, procedure date, and medical center. We compared the detection of GIM/GD using four different biopsy sampling methods: unspecified, specified stomach location, two-plus-two, and Sydney protocol. Additionally, we assessed trends in use of sampling methods (Cochrane-Armitage) and identified patient/endoscopist factors associated with their use (logistic regression). We identified a total of 20,938 GIM and 455 GD matched pairs. A greater proportion of GIM-cases were detected using two-plus-two (31.3%vs25.3%, p<0.0001) and Sydney (9.1%vs1.0%, p<0.0001) compared to controls. Similarly, a greater proportion of GD-cases were detected using Sydney (15.6%vs0.4%, p<0.0001). We observed an increasing trend in the use of the Sydney protocol during the study period (3.8% to 16.1% in cases, p<0.0001; 1% to 1.1% in controls, p=0.005). Male and Asian-American patients were more likely to undergo two-plus-two or Sydney, while female and Hispanic endoscopists were more likely to perform sampling using these protocols. The application of the Sydney protocol is associated with an increased detection of precursor lesions of gastric cancer in routine clinical practice.

Endoscopic surveillance for familial intestinal gastric cancer in low-incidence areas: An effective strategy.

While clinical practice guidelines for hereditary diffuse gastric cancer are well established, there is no consensus on the approach for familial intestinal gastric cancer (FIGC). In low-incidence gastric cancer (GC) areas such as the United States or most European countries, there are no evidence-based recommendations on endoscopic assessment in FIGC families. We aim to describe the yield of GC surveillance in these families, and to identify epidemiological risk factors for the development of GC and its precursor lesions. This is a multicenter observational study involving nine tertiary Spanish hospitals, in which all individuals fulfilling FIGC criteria who underwent endoscopic surveillance were included between 1991 and 2020. Forty-one healthy individuals of 31 families were recruited. The median number of upper gastrointestinal endoscopies per individual was 3 (interquartile range, IQR, 1-4). The median interval time between tests was 2 years (IQR 1.5-2.5), and the median follow-up was 9 years (IQR 3-14.5). In 18 (43.9%) subjects, a precursor lesion of GC was found during follow-up, and in 2 (4.9%), an early GC was identified, in which curative treatment was offered. Helicobacter pylori (Hp) infection proved to be independently associated with an increased risk of developing precursor lesions or GC, adjusted by age, gender and follow-up, with an Odds Ratio of 6.443 (1.36-30.6, P value .019). We present the first outcomes that support endoscopic surveillance with biopsies and detection of Hp in FIGC families, although the periodicity has yet to be defined.

Gastric Cancer Incidence and Mortality After Endoscopic Resection of Gastric Adenoma: A Nationwide Cohort Study.

Gastric adenoma is a precursor lesion of gastric cancer. We investigated whether the removal of gastric adenoma prevented gastric cancer incidence and its mortality. Using the linkage of nationwide databases, we assessed gastric cancer incidence and mortality among patients who had gastric adenomas removed between 2011 and 2013 in Korea. These outcomes were compared primarily with those of the Korean general population by estimating the standardized incidence and mortality ratio and secondarily with internal control subjects who did not have gastric neoplasm after esophagogastroduodenoscopy and were matched for age, sex, and calendar year by calculating hazard ratios (HR) with the Cox proportional hazards model. We identified 44,405 adenoma removal patients. During a median follow-up of 8.4 years, 1,038 (2.34%) of them were given a diagnosis of gastric cancer and a total of 524 gastric cancers were expected for a standard incidence ratio of 1.98 (95% confidence interval [CI], 1.84-2.13). A total of 199 deaths from gastric cancer were expected and 99 were observed for a standard mortality ratio of 0.50 (95% CI, 0.40-0.60). Compared with the nonadenoma cohort (n = 39,826), the adenoma removal patients had a higher risk of gastric cancer (HR, 2.84; 95% CI, 2.51-3.21) and associated mortality (HR, 1.66; 95% CI, 1.19-2.31). Removal of gastric adenoma resulted in lower-than-expected mortality but higher-than-expected incidence due to gastric cancer than that in the general population. Our analyses indicated the importance of follow-up strategy after removal of gastric adenoma.

P-141 EPIYA motif analysis of Helicobacter pylori isolated from Colombian patients with precursor lesions of gastric cancer

P-141 EPIYA motif analysis of Helicobacter pylori isolated from Colombian patients with precursor lesions of gastric cancer

P-191 Helicobacter pylori ancestors associated to gastric microbiota dysbiosis in Colombian patients with gastric cancer precursor lesions

P-191 Helicobacter pylori ancestors associated to gastric microbiota dysbiosis in Colombian patients with gastric cancer precursor lesions

Coding and non-coding co-expression network analysis identifies key modules and driver genes associated with precursor lesions of gastric cancer

BackgroundHelicobacter pylori infection is the most important risk factor for gastric cancer (GC). Human gastric adenocarcinoma develops after long-term H. pylori infection via the Correa cascade. This carcinogenic pathway describes the progression from gastritis to atrophy, intestinal metaplasia (IM), dysplasia and GC. Patients with atrophy and intestinal metaplasia are considered to have precancerous lesions of GC (PLGC). H. pylori eradication and endoscopy surveillance are currently the only interventions for preventing GC. Better knowledge of the biology of human PLGC may help find stratification markers and contribute to better understanding of biological mechanisms. One way to achieve this is by using co-expression network analysis. Weighted gene co-expression network analysis (WGCNA) is often used to identify modules from co-expression networks and relate them to clinical traits. It also allows identification of driver genes that may be critical for PLGC. AimThe purpose of this study was to identify co-expression modules and differential gene expression in dyspeptic patients at different stages of the Correa pathway. MethodsWe studied 96 gastric biopsies from 78 patients that were clinically classified as: non-active (n = 10) and chronic-active gastritis (n = 20), atrophy (n = 12), and IM (n = 36). Gene expression of coding RNAs was determined by microarrays and non-coding RNAs by RNA-seq. The WGCNA package was used for network construction, module detection, module preservation and hub and driver gene selection. ResultsWGCNA identified 20 modules for coding RNAs and 4 for each miRNA and small RNA class. Modules were associated with antrum and corpus gastric locations, chronic gastritis and IM. Notably, coding RNA modules correlated with the Correa cascade. One was associated with the presence of H. pylori. In three modules, the module eigengene (ME) gradually increased in the stages toward IM, while in three others the inverse relationship was found. One miRNA module was negatively correlated to IM and was used for a mRNA-miRNA integration analysis. WGCNA also uncovered driver genes. Driver genes show both high connectivity within a module and are significantly associated with clinical traits. Some of those genes have been previously involved in H. pylori carcinogenesis, but others are new. Lastly, using similar external transcriptomic data, we confirmed that the discovered mRNA modules were highly preserved. ConclusionOur analysis captured co-expression modules that provide valuable information to understand the pathogenesis of the progression of PLGC.

Identification of Combinations of Plasma lncRNAs and mRNAs as Potential Biomarkers for Precursor Lesions and Early Gastric Cancer.

Patients with gastric cancer (GC) are usually first diagnosed at an advanced stage due to the absence of obvious symptoms at an early GC (EGC) stage. Therefore, it is necessary to identify an effective screening method to detect precursor lesions of GC (PLGC) and EGC to increase the 5-year survival rate of patients. Cell-free RNA, as a biomarker, has shown potential in early diagnosis, personalised treatment, and prognosis of cancer. In this study, six RNAs (CEBPA-AS1, INHBA-AS1, AK001058, UCA1, PPBP, and RGS18) were analysed via real-time quantitative polymerase chain reaction (RT-qPCR) using the plasma of patients with EGC and PLGC to identify diagnostic biomarkers. The receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic accuracy. Among the six RNAs, four lncRNAs (CEBPA-AS1, INHBA-AS1, AK001058, and UCA1) were upregulated and two mRNAs (PPBP and RGS18) were downregulated in the plasma of patients with PLGC and EGC. According to the findings of the ROC analysis, the four-RNA combination of INHBA-AS1, AK001058, UCA1, and RGS18 had the highest area under the curve (AUC) value for determining risk of GC in patients with PLGC and the six-RNA combination including CEBPA-AS1, INHBA-AS1, AK001058, UCA1, PPBP, and RGS18 had the highest AUC value for determining the risk of GC in patients with EGC. The results suggest the potential usefulness of noninvasive biomarkers for the molecular diagnosis of GC at earlier stages.

Prevalence of gastric cancer precursor lesions in patients of a secondary care center in a state in south of Brazil

Background: Atrophy of the gastric mucosa and intestinal metaplasia is considered malignant precursor lesions of gastric cancer, which is considered the fifth most common neoplasm in the world and the third cause of death from cancer. The main risk factor is the infection by Helicobacter pylori (H. pylori), which increases up to six times the risk of gastric cancer, through gastritis, atrophy, and hypochlorhydria, consequences of the infection. Other risk factors are also worth noting, like smoking and a family history of gastric cancer. Objective: To investigate the prevalence of malignant precursor lesions and their associated factors in patients who underwent upper gastrointestinal endoscopy. Methods: A descriptive, observational study was performed based on an analysis of endoscopic gastric biopsies performed in two affiliated private laboratories to the Unified Health System (Sistema Único de Saúde [SUS]) in a city in Paraná state. Patients were assessed for age, sex, active or recent smoking, family history of gastric cancer, and previous treatment for H. pylori. The samples were evaluated for the presence of glandular atrophy, intestinal metaplasia, dysplasia, and H. pylori infection. Results: A total of 1,549 medical records and patient reports were evaluated and 945 were eligible, the average age was 52.2 (±14.3) years old and most patients (73.3%) were female. The prevalence of H. pylori infection was 47.5% (n= 449) and the highest percentage was between 30-39 years (58.7%). Among H. pylori-positive (+) patients who had developed intestinal metaplasia, there is more risk of having incomplete than complete metaplasia (OR: 4.34; 1.1–17.1; 95%CI). Patients who smoke are more increase the risk to developed glandular atrophy (OR: 1.91; 1.09-3.33; 95%CI) and intestinal metaplasia (OR: 1.93; 0.72-5.11; 95%CI). Conclusion: The study reinforces risk factors such as smoking and H. pylori infection as precursors for developing pre-neoplastic lesions in a population in southern Brazil, highlighting the importance of smoking cessation and prevention of H. pylori infection and the treatment of infected patients.

&amp;lt;i&amp;gt;Helicobacter pylori&amp;lt;/i&amp;gt; Infection and Gastroduodenal Lesions: Prevalence and Associated Factors in Cote d’Ivoire

Objective: The objective is to determine the prevalence of Helicobacter pylori (Hp) infection and highlight the determinants of the infection as well as the gastric histopathological lesions associated with this infection. Methods: This is a retrospective study carried out from August 01, 2015 to December 31, 2020 in Bouaké. It included all patients with gastric and/or duodenal lesion on upper gastrointestinal endoscopy in whom gastric biopsies and histopathology results are available. Results: The study involved 510 patients (301 men and 209 women). The prevalence of Hp was 66.47% (339/510 patients). The presence of Hp was not significantly related to age and gender. Epigastralgia was the most common indication with no significant difference between the positive and negative Hp groups (65.37% vs 34.63%, p = 0.35). A significant difference was only observed for duodenal ulcers (84.31% Hp+ vs 15.69% Hp-, p = 0.004). Regarding histological lesions: Chronic and active gastritis was strongly related to the presence of Hp (p Hp. These precursor lesions of gastric cancer (metaplasia and atrophy) were, however, significantly related to chronic gastric disease with p = 0.02 and p Conclusion: The prevalence of Hp is high in Bouaké. Our study confirms the link between Hp infection and chronic and active gastritis.

Rescue Therapy with Furazolidone in Patients with at Least Five Eradication Treatment Failures and Multi-Resistant H. pylori infection.

Helicobacter pylori infection may persist after multiple eradication treatments. The aim of this study was to evaluate the efficacy and safety of a furazolidone-based rescue regimen in hyper-refractory patients. A unicentre, prospective study was designed. Patients in whom five or more treatments had consecutively failed were included. All patients had previously received bismuth and key antibiotics, such as amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin, and had positive H. pylori culture, demonstrating resistance to clarithromycin, metronidazole, and levofloxacin. A quadruple regimen with furazolidone (200 mg), amoxicillin (1 g), bismuth (240 mg), and esomeprazole (40 mg) was prescribed twice a day for 14 days. Eradication was confirmed by the stool antigen test. Compliance was determined through questioning, and adverse effects using a questionnaire. Eight patients (mean age 56 years, 63% men, 38% peptic ulcer disease, 12% gastric cancer precursor lesions, and 50% functional dyspepsia) were included. Per-protocol and intention-to-treat eradication rates were 63%. Compliance was 100%. Adverse effects were reported in two (25%) patients, and all were mild. Even after five or more previous H. pylori eradication failures, and a multi-resistant infection, rescue treatment with furazolidone may be effective in approximately two-thirds of the cases, constituting a valid strategy after multiple previous eradication failures with key antibiotics such as clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin.

Quality in diagnostic upper gastrointestinal endoscopy for the detection and surveillance of gastric cancer precursor lesions: Position paper of AEG, SEED and SEAP

This position paper, sponsored by the Asociación Española de Gastroenterología [Spanish Association of Gastroenterology], the Sociedad Española de Endoscopia Digestiva [Spanish Gastrointestinal Endoscopy Society] y the Sociedad Española de Anatomía Patológica [Spanish Anatomical Pathology Society], aims to establish recommendations for performing an high quality upper gastrointestinal endoscopy for the screening of Gastric Cancer Precursor Lesions (GCPL) in low-incidence populations, such as the Spanish population. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates different measures to improve the quality of upper gastrointestinal endoscopy in this setting and makes recommendations on how to evaluate and treat the identified lesions. We recommend that upper gastrointestinal endoscopy for surveillance of GCPL should be performed by endoscopists with adequate training, administering oral premedication and use of sedation. To improve the identification of GCPL, we recommend the use of high definition endoscopes and conventional or digital chromoendoscopy and, for biopsies, NBI should be used to target the most suspicious areas of intestinal metaplasia. Regarding the evaluation of visible lesions, the risk of submucosal invasion should be evaluated with magnifying endoscopes and endoscopic ultrasound should be reserved for those with suspected deep invasion. In lesions amenable to endoscopic resection, submucosal endoscopic dissection is considered the technique of choice. Este documento de posicionamiento, auspiciado por la Asociación Española de Gastroenterología, la Sociedad Española de Endoscopia Digestiva y la Sociedad Española de Anatomía Patológica tiene como objetivo establecer recomendaciones para realizar una endoscopia digestiva (EDA) de calidad en la detección y vigilancia de lesiones precursoras de cáncer gástrico (LPCG) en poblaciones con incidencia baja, como la española. Para establecer la calidad de la evidencia y los niveles de recomendación se ha utilizado la metodología basada en el sistema GRADE ( Grading of Recommendations Assessment, Development and Evaluation) . Se obtuvo el consenso entre expertos mediante un método Delphi. El documento evalúa diferentes medidas para mejorar la calidad de la EDA en este contexto y hace recomendaciones de cómo evaluar y tratar las lesiones identificadas. Se recomienda que la EDA de vigilancia de LPCG sea realizada por endoscopistas con capacitación adecuada, administrando premedicación oral y uso de sedación. Para mejorar la identificación de LPCG se recomienda el uso de endoscopios de alta definición y cromoendoscopia convencional o digital y, para las biopsias, debe utilizarse el NBI para dirigirlas a las áreas más sospechosas de metaplasia intestinal. En cuanto a la evaluación de las lesiones visibles, el riesgo de invasión de la submucosa debe evaluarse con endoscopios de magnificación y reservar la ecoendoscopia para aquellas con sospecha de invasión profunda. En las lesiones susceptibles de resección endoscópica, la disección endoscópica submucosa se considera la técnica de elección.

Gastric cancer screening in low incidence populations: Position statement of AEG, SEED and SEAP

This positioning document, sponsored by the Asociacion Espanola de Gastroenterologia, the Sociedad Espanola de Endoscopia Digestiva and the Sociedad Espanola de Anatomia Patologica, aims to establish recommendations for the screening of gastric cancer (GC) in low incidence populations, such as the Spanish. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates screening in the general population, individuals with relatives with GC and subjects with GC precursor lesions (GCPL). The goal of the interventions should be to reduce GC related mortality. We recommend the use of the OLGIM classification and determine the intestinal metaplasia (IM) subtype in the evaluation of GCPL. We do not recommend to establish endoscopic mass screening for GC or Helicobacter pylori. However, the document strongly recommends to treat H.pylori if the infection is detected, and the investigation and treatment in individuals with a family history of GC or with GCPL. Instead, we recommend against the use of serological tests to detect GCPL. Endoscopic screening is suggested only in individuals that meet familial GC criteria. As for individuals with GCPL, endoscopic surveillance is only suggested in extensive IM associated with additional risk factors (incomplete IM and/or a family history of GC), after resection of dysplastic lesions or in patients with dysplasia without visible lesion after a high quality gastroscopy with chromoendoscopy.

Associations of Duration, Intensity, and Quantity of Smoking With Risk of Gastric Intestinal Metaplasia.

Determine whether various dimensions of smoking increase risk for gastric intestinal metaplasia. Cigarette smoking has been implicated in the etiology of gastric cancer, but it is not clear if smoking is a risk factor for gastric intestinal metaplasia, a precursor lesion of gastric cancer. We compared data from 385 gastric intestinal metaplasia cases and 1577 controls without gastric intestinal metaplasia recruited into a cross-sectional study at the Michael E. DeBakey VA Medical Center in Houston, Texas. All participants completed standardized questionnaires and underwent a study endoscopy with gastric mapping biopsies. Gastric intestinal metaplasia cases included participants with intestinal metaplasia on any noncardia gastric biopsy. We calculated odds ratios and associated 95% confidence intervals using multivariable logistic regression models. Compared with never smokers, current smokers had 2-fold increased risk for gastric intestinal metaplasia (odds ratio, 2.05; 95% confidence interval, 1.47-2.85). Among ever smokers, increasing duration and total dose were significantly associated with increased risk for gastric intestinal metaplasia (P-trend, 0.004 and 0.01, respectively). Among former smokers, risk for gastric intestinal metaplasia decreased over time and was no different to never smokers after 15 years smoking cessation. Cases with gastric intestinal metaplasia were more likely than controls to have Helicobacter pylori infection (53.2% vs. 21.7%); however, smoking effect on gastric intestinal metaplasia was not different by H. pylori infection status. Cigarette smoking is a risk factor for gastric intestinal metaplasia. Risk of gastric intestinal metaplasia among former smokers remained significantly elevated until 15 years postcessation.

High frequency of gastric cancer precursor lesions in patients with gastric xanthelasma: a prospective case-control study.

An association of gastric cancer and precursor lesions with gastric xanthelasma has frequently been reported. However, the incidence of both gastric xanthelasma and gastric cancer precursor lesions increases with age. The aim of this study was to evaluate the frequency and characteristics of atrophic gastritis, intestinal metaplasia and dysplasia in patients with gastric xanthelasma compared to controls. Cases with gastric xanthelasma endoscopically and histopathologically were included in this prospective study. The patients included in the study were compared with age- and sex-matched controls in terms of the frequency and characteristics of atrophic gastritis, intestinal metaplasia, dysplasia and cancer. In a series of 1892 upper endoscopies, 108 patients (5.7%) were found to have gastric xanthelasma. The average age of the patients was 61.41 ± 11.43 years. Among the patients, 58 (53.7%) were male. The frequencies of atrophic gastritis, intestinal metaplasia, dysplasia and gastric cancer in the xanthelasma group (n = 108) were 31.5, 68.5, 3.7 and 2.8%, respectively. The frequencies of atrophic gastritis, intestinal metaplasia, dysplasia and gastric cancer in the control group (n = 183) were 11.5, 31.7, 0.5 and 0.5%, respectively. Compared to the control group, the frequency of these cancer precursor lesions and the prevalence of advanced stage based on operative link on gastritis intestinal metaplasia assessment were found to be higher in the xanthelasma group (P < 0.05). Gastric xanthelasma is associated with an increased frequency of gastric precancerous lesions and should be considered an important marker.

Natural Course of Atrophic Gastritis and Intestinal Metaplasia

Atrophic gastritis (AG) and intestinal metaplasia (IM) are considered the main precursor lesions of gastric cancer, and the risk of gastric cancer in the gastric mucosa increases in the presence of AG and IM. The development of intestinal-type gastric adenocarcinoma represents the last step of an inflammation-metaplasia-dysplasia-carcinoma sequence, called the Correa cascade of multistep gastric carcinogenesis. The incidences of both AG and IM tend to increase with age. &lt;i&gt;Helicobacter pylori&lt;/i&gt; is regarded the most important factor in the development of IM; the progression of AG to IM is also affected by numerous environmental factors and individual genetic factors. Therefore, understanding the natural course of AG and IM is very important, especially in areas with a high prevalence of gastric cancer such as Korea.

MicroRNA-30a arbitrates intestinal-type early gastric carcinogenesis by directly targeting ITGA2.

Spasmolytic polypeptide-expressing metaplasia (SPEM) is considered a precursor lesion of intestinal metaplasia and intestinal-type gastric cancer (GC), but little is known about microRNA alterations during metaplasia and GC developments. Here, we investigate miR-30a expression in gastric lesions and identify its novel target gene which is associated with the intestinal-type GC. We conducted in situ hybridization and qRT-PCR to determine miR-30a expression in gastric tissues. miR-30a functions were determined through induction or inhibition of miR-30a in GC cell lines. A gene microarray was utilized to confirm miR-30a target genes in GC, and siRNA-mediated target gene suppression and immunostaining were performed. The Cancer Genome Atlas data were utilized to validate gene expressions. We found down-regulation of miR-30a during chief cell transdifferentiation into SPEM. MiR-30a level was also reduced in the early stage of GC, and its level was maintained in advanced GC. We identified a novel target gene of miR-30a and ITGA2, and our results showed that either ectopic expression of miR-30a or ITGA2 knockdown suppressed GC cell proliferation, migration, and tumorigenesis. Levels of ITGA2 inversely correlated with levels of miR-30a in human intestinal-type GC. We found down-regulation of miR-30a in preneoplastic lesions and its tumor-suppressive functions by targeting ITGA2 in GC. The level of ITGA2, which functions as an oncogene, was up-regulated in human GC. The results of this study suggest that coordination of the miR-30a-ITGA2 axis may serve as an important mechanism in the development of gastric precancerous lesions and intestinal-type GC.

HELICOBACTER PYLORI INFECTION AND GASTRIC CANCER PRECURSOR LESIONS: PREVALENCE AND ASSOCIATED FACTORS IN A REFERENCE LABORATORY IN SOUTHEASTERN BRAZIL

Helicobacter pylori infection is the most important risk factor for gastric atrophy and intestinal metaplasia, both considered gastric cancer precursor lesions. Therefore, the investigation of the occurrence of H. pylori infection, precursor lesions and associated factors guides the adoption of specific strategies for the control this type of cancer. To evaluate the prevalence of H. pylori infection in patients undergoing upper digestive endoscopy, as well as the prevalence of intestinal metaplasia, atrophy and chronic inflammation and their association with H. pylori infection. A retrospective study was performed based on reports of gastric endoscopic biopsies performed in a private laboratory affiliated to the Brazilian Public Health System (SUS). Patients were evaluated for age, gender and type of health service. The samples were evaluated for the presence of H. pylori, and also of chronic inflammation, intestinal metaplasia and glandular atrophy. Of a total of 4,604 patients (mean age 51±16.6), 63.9% were female and 63.1% coming from private health care service. The prevalence of H. pylori infection was 31.7% (n=1,459), and the percentage of infection was significantly higher in patients from public health service (42.0%) in relation to patients from private health service (25.6%). Among H. pylori (+) patients, a higher percentage of intestinal metaplasia (17.7% vs 13.3%) and glandular atrophy (17.6% vs 6.9%) were observed when compared to those H. pylori (-) (P<0.01). From the patients H. pylori (+) with at least one type of precursor lesion (n=418), 161 (38.5%) had metaplasia and chronic inflammation, 160 (38.3%) had atrophy and chronic inflammation and finally 97 (23.2%) presented metaplasia, atrophy and chronic inflammation simultaneously. The present study reinforces the association of H. pylori infection with gastric cancer precursor lesions in a Brazilian population, emphasizing the importance of infection prevention measures, as well as the treatment of infected patients, especially in regions with lower socioeconomic levels that show a higher prevalence of infection by H. pylori.