Combination detection of IgG- and IgA-related autoantibodies for the early diagnosis of gastric cancer.

Regulation of Gastric Carcinogenesis by InflammatoryCytokines.

BackgroundThis study aimed to explore the diagnostic value of serum miR-101-3p combined with pepsinogen (PG) on early diagnosis of gastric cancer (GC).MethodsA total of 61 atrophic gastritis (AG) and 86 GC patients, and 50 healthy volunteers were enrolled. The serum expression of miR-101-3p was measured by qRT-PCR. The serum content of carcinoembryonic antigen (CEA) was measured by Electrochemiluminescence immunoassay. The serum contents of PGI and PGII were measured by Enzyme linked immunosorbent assay. The diagnostic value of serum markers on AG and GC was analyzed by receiver operating characteristic (ROC) analysis.ResultsThe expression of miR-101-3p, the content of PGI and the ratio of PGI/II were significantly decreased, and the content of PGII was significantly increased in AG patients compared with those in normal controls. The changes of the above serum indicators were more obvious in GC patients than those in AG patients. The content of CEA was significantly higher in GC patients than that in AG patients. In addition, the expression of miR-101-3p was negatively associated with the submucosal infiltration in GC patients. MiR-101-3p exhibited high diagnostic value on AG (AUC 0.8493, sensitivity 80.33%, specificity 80%) and GC (AUC 0.8749, sensitivity 72.09%, specificity 86.49%). MiR-101-3p + PGI + PGI/II (AUC 0.856, sensitivity 80.23%, specificity 77.05%) exhibited a high diagnostic value in distinguishing between AG and GC.ConclusionsMiR-101-3p was a potential diagnostic marker for AG and GC. MiR-101-3p + PGI + PGI/II was effective in distinguishing between AG and GC.

Diagnostic value of combined detection of three gastric functions and Helicobacter pylori typing in chronic gastritis and gastric cancer

Chronic Helicobacter pylori infection produces several lesions in the human stomach, which can progress to chronic atrophic gastritis and gastric cancer. To date, there is very little information on gene expression in chronic atrophic gastritis and its relationship with progression to gastric cancer. In this study, we performed a gene expression analysis during chronic atrophic gastritis in order to identify possible biomarkers that allow an early diagnosis of gastric cancer. We studied biopsies from patients with chronic atrophic gastritis and gastric cancer. The biopsies were analyzed by a gene expression microarray and corroborated by qPCR and validated through immunohistochemistry. Our results revealed that gene expression profiles in patients with chronic atrophic gastritis showed molecular changes of the gastric mucosa, leading to gastric cancer. The gene expression profiles of CLDN1, CLDN7, OLFM4, C-MYC and MMP9 were more notable from the chronic atrophic gastritis. The gene expression patterns observed in this study allowed the identification of CLDN1 and MMP9 proteins as promising biomarkers of early stages of gastric cancer development.

How to Manage a Patient With Gastric Intestinal Metaplasia: An International Perspective

Gastric cancer continues to be a significant global healthcare challenge, and its burden remains substantial. The development of gastric cancer (GC) is closely linked to chronic atrophic gastritis (CAG), yet there is a scarcity of research exploring the underlying mechanisms of CAG-induced carcinogenesis. In this study, we conducted a comprehensive investigation into the oncogenes involved in CAG using both bulk transcriptome and single-cell transcriptome data. Our approach employed hdWGCNA to identify pathogenic genes specific to CAG, with non-atrophic gastritis (NAG) serving as the control group. Additionally, we compared CAG with GC, using normal gastric tissue as the control group in the single-cell transcriptome analysis. By intersecting the identified pathogenic genes, we pinpointed key network molecules through protein interaction network analysis. To further refine the gene selection, we applied LASSO, SVM-RFE, and RF techniques, which resulted in a set of cancer-related genes (CRGs) associated with CAG. To identify CRGs potentially linked to gastric cancer progression, we performed a univariate COX regression analysis on the gene set. Subsequently, we explored the relationship between CRGs and immune infiltration, drug sensitivity, and clinical characteristics in gastric cancer patients. We employed GSVA to investigate how CRGs regulated signaling pathways in gastric cancer cells, while an analysis of cell communication shed light on the impact of CRGs on signal transmission within the gastric cancer tumor microenvironment. Lastly, we analyzed changes in metabolic pathways throughout the progression of gastric cancer. Using hdWGCNA, we have identified a total of 143 pathogenic genes that were shared by CAG and GC. To further investigate the underlying mechanisms, we conducted protein interaction network analysis and employed machine learning screening techniques. As a result, we have identified 15 oncogenes that are specifically associated with chronic atrophic gastritis. By performing ROC reanalysis and prognostic analysis, we have determined that GADD45B is the most significant gene involved in the carcinogenesis of CAG. Immunohistochemical staining and differential analysis have revealed that GADD45B expression was low in GC tissues while high in normal gastric tissues. Moreover, based on prognostic analysis, high expression of GADD45B has been correlated with poor prognosis in GC patients. Additionally, an analysis of immune infiltration has shown a relationship between GADD45B and the infiltration of various immune cells. By correlating GADD45B with clinical characteristics, we have found that it primarily affects the depth of invasion in GC. Through cell communication analysis, we have discovered that the CD99 signaling pathway network and the CDH signaling pathway network are the main communication pathways that significantly alter the microenvironment of gastric tissue during the development of chronic atrophic gastritis. Specifically, GADD45B-low GC cells were predominantly involved in the network communication of the CDH signaling pathway, while GADD45B-high GC cells played a crucial role in both signaling pathways. Furthermore, we have identified several metabolic pathways, including D-Glutamine and D-glutamate metabolism and N-Glycan biosynthesis, among others, that played important roles in the occurrence and progression of GC, in addition to the six other metabolic pathways. In summary, our study highlighted the discovery of 143 pathogenic genes shared by CAG and GC, with a specific focus on 15 oncogenes associated with CAG. We have identified GADD45B as the most important gene in the carcinogenesis of CAG, which exhibited differential expression in GC tissues compared to normal gastric tissues. Moreover, GADD45B expression was correlated with patient prognosis and is associated with immune cell infiltration. Our findings also emphasized the impact of the CD99 and CDH signaling pathway networks on the microenvironment of gastric tissue during the development of CAG. Additionally, we have identified key metabolic pathways involved in GC progression. GADD45B, an oncogene implicated in chronic atrophic gastritis, played a critical role in GC development. Decreased expression of GADD45B was associated with the onset of GC. Moreover, GADD45B expression levels were closely tied to poor prognosis in GC patients, influencing the infiltration patterns of various cells within the tumor microenvironment, as well as impacting the metabolic pathways involved in GC progression.

ObjectiveMicrobial infections have been shown to contribute to gastric carcinogenesis, the knowledge of gastric microbiota alteration in this process may provide help in early diagnosis of gastric cancer. The aim of this study was to characterize the microbial changes and identify taxonomic biomarkers across stages of gastric carcinogenesis.MethodsThe gastric microbiota was investigated by 16S rRNA gene analysis in gastric mucosal specimens from 47 patients including superficial gastritis (SG), atrophic gastritis (AG), gastric intraepithelial neoplasia (GIN), and gastric cancer (GC). Differences in microbial composition across the disease stages, especially in GIN and GC were assessed using linear discriminant analysis effect size.ResultsThere was no gradual changing trend in the richness or diversity of the gastric microbiota across stages of gastric carcinogenesis. The relative abundance of dominant taxa at phylum and genus levels didn’t show a gradual shift pattern, and the only four taxa that continuously enriched from SG to GC were Slackia, Selenomonas, Bergeyella, and Capnocytophaga, all of which were oral bacteria. The most representative taxa which were enriched in GC patients were oral bacteria including Parvimonas, Eikenella and Prevotella-2, and environmental bacteria including Kroppenstedtia, Lentibacillus, and Oceanobacillus. The gastric microbiota in GIN patients were characterized by enrichment of intestinal commensals including Romboutsia, Fusicatenibacter, Prevotellaceae-Ga6A1-group, and Intestinimonas. Gastric cardia cancer and non-cardia cancer patients had significantly different microbiota profiles characterized by a higher abundance of Helicobacter in the cardia cancer patients.ConclusionsOur results provide insights on potential taxonomic biomarkers for gastric cancer and precancerous stages, and suggest that gastric microbiota might play different roles in the carcinogenesis of cardia cancer and non-cardia cancer.

To screen and identify the serum specific protein markers of patients with gastric cancer by proteomics technology, and to provide more comprehensive serum protein fingerprint model for the early diagnosis of gastric cancer. Preoperative and postoperative blood samples were collected from 60 gastric cancer patients. Mass spectrometry (SELDI-TOF-MS) technology was used to detect and screen serum specific proteins in gastric cancer patients(preoperative group, postoperative group, metastasis group), and the result was compared with normal control group. Gel electrophoresis(TRICINE SDS-OAGE) technology was applied in the separation and purification for those different protein. Matrix assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF) technology was used in the identification for the proteins following separation and purification. Mass spectrometry data of preoperative group and normal group resulted in 15 specific m/z peak(P<0.01). SVM screened by a combination of the highest index model Youden get m/z peak at 6 449.1 protein markers. The protein expression of preoperative group was significantly higher than that of normal group(2 299.3±2 029.3 vs. 509.5±168.3, P<0.01). Mass spectrometry data of preoperative group and postoperative group resulted in 6 specific m/z peak(P<0.01). SVM screened by a combination of the highest Youden index model indentified get m/z peak at 6 449.2 protein markers. The protein expression of preoperative group was significantly higher than that of postoperative group(1 247.9±685.0 vs. 476.5±157.8, P<0.01). Mass spectrometry data of preoperative group and metastasis group resulted in 12 specific m/z peak (P<0.01). SVM screened by a combination of the highest Youden index model indentified get m/z peak at 6 448.9 protein markers. The protein expression of metastasis group was higher than that of preoperative group(1 506.9±1 036.5 vs. 649.7±621.0). MALDI-TOF/TOF identified that the protein with m/z peak at 6 449 was Apo CIII(. Apo CIII( may be the specific serum protein marker of gastric cancer, which may provide a more comprehensive serum protein fingerprint model for the early diagnosis of gastric cancer and a new way for further research.

BackgroundThe present study aimed to identify a specific circular RNA (circRNA) for early diagnosis of gastric cancer (GC).MethodsTotally 82 patients with GC, 30 with chronic nonatrophic gastritis and 30 with chronic atrophic gastritis were included in this study. Four of the 82 GC patients were selected for screening. Total RNA from malignant and adjacent tissue samples was extracted, and circRNAs in four patients were screened. According to the screening results, the eight most upregulated and downregulated circRNAs with a statistically significant association with GC were identified by real-time fluorescent quantitative polymerase chain reaction (PCR). Then, the most regulated circRNA was selected for further sensitivity and specificity assessments. CircRNA expression was examined by quantitative reverse transcriptase PCR in 78 GC (21 and 57 early and advanced GC, respectively) and adjacent tissue samples, as well as in gastric fluid samples from 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, and 78 GC.ResultsA total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significantly altered expression in GC tissue samples. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissue samples, with levels in GC tissue samples correlating with tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen amounts, and carbohydrate antigen 19–9 levels. Strikingly, this circRNA was found in the gastric fluid of patients with early and advanced GC.ConclusionsThe present study uncovered a new circRNA expression profile in human GC, with hsa_circ_000780 significantly downregulated in GC tissue and gastric fluid specimens. These findings indicate that hsa_circ_000780 should be considered a novel biomarker for early GC screening.

The risk of gastric cancer (GCA) is increased in atrophic gastritis. A low serum pepsinogen group I (SPGI) level is a good serologic indicator of atrophic gastritis of the gastric corpus and fundus, and can be used for diagnosis of subjects with atrophic gastritis and of increased risk for GCA. The present study was undertaken to investigate whether SPGI assay and a diagnostic gastroscopy could enable the diagnosis of GCA at an early stage. The study was carried out as part of the Alpha-Tocopherol, Beta-Carotene Cancer prevention study (ATBC study) in Finland, in which 22,436 male smokers aged 50-69 years were screened by SPGI. Low SPGI levels (< 25 microg/l) were found in 2196 (9.8%) men. Upper GI endoscopy (gastroscopy) was performed in 1344 men (61%) and 78% of these had moderate or severe atrophic corpus gastritis in endoscopic biopsies. A control series of 136 men from the ATBC study cohort with abdominal symptoms, but with SPGI > or = 50 microg/l were similarly endoscopied, and 2.2% of these had corpus atrophy. Neoplastic alterations were found in 63 (4.7%; 95% CI: 3.6%-5.8%) of the 1344 endoscopied men with low SPGI levels. Of these, 42 were definite dysplasias of low grade, 7 dysplasias of high grade, 11 invasive carcinomas, of which 7 were 'early' cancers, and 3 carcinoid tumors. In the control series, 1 man (0.7%) of the 136 men had a definite low-grade dysplasia. Thus, 18 (1.3%; 95% CI 0.7%-2.0%) cases with 'severe' neoplastic lesions (4 advanced cancers, 7 early cancers and 7 dysplasias of high grade) were found in the low SPGI group, but there were none in the control group. All four patients with advanced cancer died from the malignancy within 5 years (mean survival time 2.5 years), whereas surgical treatment in all those with early cancer or high-grade dysplasia was curative. One of the seven patients with early cancer and two of the seven with high-grade dysplasia died within 5 years, but none died from the gastric cancer. Thus, curative treatment was given to 14 of 18 men in whom a malignant lesion was found in gastroscopy. This is about 15% of all gastric cancer cases (92 cases) which were diagnosed within 5 years after SPGI screening in the 22,436 men. Among the gastric cancer cases of the main ATBC study, the 5-year survival rate was 33% (85% of the non-survivors died from gastric cancer). We conclude that assay of SPGI followed by endoscopy is an approach which can enable the early diagnosis of gastric cancer at a curable stage.

Magnifying endoscopy for the diagnosis of early gastric cancer: Establishment of technique, diagnostic system, and scientific evidence from Japan

Objective To detect serum level of long noncoding RNA (lncRNA) BC200 in gastric cancer(GC) patients, and investigate its relationship with clinical features, and evaluate its diagnostic value for GC. Methods A case-control study was performed. From November 2014 to July 2015, serum levels of lncRNA BC200 were detected by real-time quantitative polymerase chain reaction in 124 patients with GC, 41 patients with atrophic gastritis and 59 normal controls who were hospitalized in Qilu Hospital of Shandong University. Meanwhile, serum carcinoembryonic antigen (CEA) and carbohydrate antigen 72-4 (CA72-4) were detected by electrochemical luminescence immunoassay. Serum levels of lncRNA BC200, before and 3, 7, 10, 30, 100 days after radical operation in another 31 patients with GC were determined. The sensitivity and specificity of serum lncRNA BC200, CEA and CA72-4 were analyzed by using of the receiver operating characteristic (ROC) curve. The comparison between two groups was performed with Mann-Whitney U test and the comparison among many groups was conducted with Kruskal-Wallis H test. Results Serum levels of lncRNA BC200 in GC patients with stage Ⅰ and Ⅱ[1.041(0.794, 1.462)]and stage Ⅲ and Ⅳ[1.290(0.978, 1.794)]were significantly higher than those in patients with precancerous lesion[0.969(0.699, 1.219)]and normal controls[0.801(0.556, 1.599)](H=54.68, P<0.000 1). Compared with pre-operation[1.120(0.859, 1.663)], the serum BC200 levels decreased significantly in 10 days[0.903(0.724, 1.182)](U=55.0, P<0.000 1), 30 days[0.759(0.671, 1.037)](U=299.0, P=0.026 1), and 100 days[0.478(0.378, 0.635)](U=41.0, P<0.000 1) after surgery. The area under the receiver operating characteristics curve(AUC) of serum lncRNA BC200 was 0.865 for GC diagnosis, which was significantly higher than that of serum CA72-4(AUC=0.699)or CEA(AUC=0.807). The AUC of combined detection of three tests was 0.934. Conclusion Serum lncRNA BC200 levels are significantly increased in GC patients, which may be used as a potential biomarker in GC diagnosis and monitoring.(Chin J Lab Med, 2017, 40: 138-142) Key words: Stomach neoplasms; RNA, long noncoding; Tumor markers, biological

Background: Most researchers point to a decrease in immunity indicators in patients with gastric cancer. At the same time, there are ambiguous interactions between tumor growth and the functioning of the immune system. Identifying gastric cancer patients at an early and curable stage of the disease is essential if the mortality rates for this disease are to decrease. The only way to prevent the development of gastric cancer is the potential reversibility of precancerous changes in the gastric mucosa. The early diagnosis of chronic atrophic gastritis is a preventive measure and it should be carried out in both the presence and absence of the symptoms of dyspepsia. Methods: A total of 299 blood samples were collected, inclusive of 98 gastric cancer patients, 104 healthy controls, and 97 patients with chronic atrophic gastritis. An evaluation of spontaneous and induced chemiluminescence (CL) was carried out for 90 minutes using a 36-channel biochemiluminometer "BLM — 3607" (Russia), and an Olympus fluorescence microscope was used for cell counting. Interpretation &amp; conclusions: Our study showed the significance of the parameters, specifically the maximum intensity of spontaneous (Ispont) and induced chemiluminescence (Iindus) of the neutrophils and monocytes, the indices of granulocytic and monocytic phagocytosis, malondialdehyde (MDA), and the ratio of the activity of the enzyme superoxide dismutase to glutathione/CAT ratio superoxide dismutase to glutathione peroxidase (SOD/GPO) in the diagnosis of early gastric cancer. Using the threshold values ​​of the proposed criteria in the screening of the adult population, it is possible to form a group that is at a high risk of developing early gastric cancer and to achieve a decrease in the mortality and disability rates in the population of Siberia. This is as well as allowing for the choosing of a more personalized therapy for the patients at a high risk of developing early gastric cancer.

Objective To evaluate the value of serum pepsinogen (PG) on atrophic gastritis and gastric cancer screening and to explore the best cut-off values of serum pepsinogen for atrophic gastritis screening in Weihai City. Methods Three hundred and sev-enty-four patients with gastroduodenal diseases were recruited, and these patients were divided into 4 groups based on endoscopic and histopathological findings:chronic superficial gastritis (CSG) group, chronic atrophic gastritis (CAG) group, gastric cancer (GC) group, and peptic ulcer (PU) group. The serum pepsinogen was detected by immunoturbidimetry. Results The PGI level and the PG Ⅰ/PGⅡ ratio (PGR) were significantly decreased in GC and CAG groups (P<0.01). The PGI level and PGR in GC and atrophic cor-pus gastritis groups were significantly different from the ones in atrophic antral gastritis group (P<0.01). The best cut-off values of the serum PGI and PGR for the atrophic gastritis screening were 76.50 ng/ml and 3.68, respectively. Conclusion The serum PGI and PGR automatic detection by immunoturbidimetry could be useful for screening gastric cancer and atrophic gastritis patients, and serum PGⅠ< 76. 50 ng/ml and PGR < 3.68 were the best cut-off values for atrophic gastritis screening in Weihai City. Key words: Pepsinogen; Atrophic gastritis; Gastric cancer; Immtmoturbidimetry; Best cut-off value

BACKGROUNDGastric cancer (GC) is one of the most frequently diagnosed tumor globally. In most cases, GC develops in a stepwise manner from chronic gastritis or atrophic gastritis (AG) to cancer. One of the major issues in clinical settings of GC is diagnosis at advanced disease stages resulting in poor prognosis. MicroRNAs (miRNAs) are small noncoding molecules that play an essential role in a variety of fundamental biological processes. However, clinical potential of miRNA profiling in the gastric cancerogenesis, especially in premalignant GC cases, remains unclear.AIMTo evaluate the AG and GC tissue miRNomes and identify specific miRNAs’ potential for clinical applications (e.g., non-invasive diagnostics).METHODSStudy included a total of 125 subjects: Controls (CON), AG, and GC patients. All study subjects were recruited at the Departments of Surgery or Gastroenterology, Hospital of Lithuanian University of Health Sciences and divided into the profiling (n = 60) and validation (n = 65) cohorts. Total RNA isolated from tissue samples was used for preparation of small RNA sequencing libraries and profiled using next-generation sequencing (NGS). Based on NGS data, deregulated miRNAs hsa-miR-129-1-3p and hsa-miR-196a-5p were analyzed in plasma samples of independent cohort consisting of CON, AG, and GC patients. Expression level of hsa-miR-129-1-3p and hsa-miR-196a-5p was determined using the quantitative real-time polymerase chain reaction and 2-ΔΔCt method.RESULTSResults of tissue analysis revealed 20 differentially expressed miRNAs in AG group compared to CON group, 129 deregulated miRNAs in GC compared to CON, and 99 altered miRNAs comparing GC and AG groups. Only 2 miRNAs (hsa-miR-129-1-3p and hsa-miR-196a-5p) were identified to be step-wise deregulated in healthy-premalignant-malignant sequence. Area under the curve (AUC)-receiver operating characteristic analysis revealed that expression level of hsa-miR-196a-5p is significant for discrimination of CON vs AG, CON vs GC and AG vs GC and resulted in AUCs: 88.0%, 93.1% and 66.3%, respectively. Compar-ing results in tissue and plasma samples, hsa-miR-129-1-3p was significantly down-regulated in GC compared to AG (P = 0.0021 and P = 0.024, tissue and plasma, respectively). Moreover, analysis revealed that hsa-miR-215-3p/5p and hsa-miR-934 were significantly deregulated in GC based on Helicobacter pylori (H. pylori) infection status [log2 fold change (FC) = -4.52, P-adjusted = 0.02; log2FC = -4.00, P-adjusted = 0.02; log2FC = 6.09, P-adjusted = 0.02, respectively].CONCLUSIONComprehensive miRNome study provides evidence for gradual deregulation of hsa-miR-196a-5p and hsa-miR-129-1-3p in gastric carcinogenesis and found hsa-miR-215-3p/5p and hsa-miR-934 to be significantly deregulated in H. pylori carrying GC patients.