Alterations in Gastric Mucosal Microbiota in Gastric Carcinogenesis: A Systematic Review and Meta-Analysis

Background: The gastric microbiota profile alters during gastric carcinogenesis. We aimed to identify the alterations in the alpha diversity and relative abundance of bacterial phyla and genera of gastric microbiota in the development of gastric cancer (GC).Methods: The systematic review was performed based on a published protocol with the registration number CRD42020206973. We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (May 2021) for observational studies reporting either the relative abundance of bacterial phyla or genera, or alpha diversity indexes in both GC and non-cancer groups. Selection of studies and data extraction were performed independently by two researchers, with disagreements resolved through discussion. Risk of bias was assessed using the self-modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD).Results: Our systematic review included 751 GC patients and 792 non-cancer patients from 14 case-control studies. Gastric cancer group had fewer operational taxonomic units (OTUs) (MD = −68.52, 95%CI: −126.65 to −10.39) and a lower Simpson index (MD = −0.13, 95%CI: −0.20 to −0.07) compared with non-cancer group. At the phylum level, gastric cancer group had a higher abundance of Firmicutes (MD = 7.11, 95%CI: 1.76 to 12.46). At the genus level, Streptococcus (MD = 3.03, 95%CI: 0.07 to 6.00) and Lactobacillus (MD = 5.15, 95%CI: 1.27 to 9.04) were found to be enriched in GCgroup. The relative abundance of the rest bacterial phyla or genera analyzed in our study did not significantly differ between two groups. Subgroup analyses indicated that the source of samples was the major source of interstudy heterogeneity.Conclusion: This systematic review suggested that gastric microbiota dysbiosis occurred in gastric carcinogenesis, with alpha diversity declined and microbiota composition altered.

Increased Oxidative Stress in Gastric Cancer Patients and Their First-Degree Relatives: A Prospective Study from North-Eastern Brazil

Background and Aims. First-degree relatives of gastric cancer patients are at increased risk of developing gastric cancer. Increased oxidative stress, including lipid peroxidation, has been associated with gastric carcinogenesis. Whether first-degree relatives of gastric cancer patients have increased oxidative stress remains unknown. We aimed to compare oxidative stress in patients with gastric cancer, their first-degree relatives, and dyspeptic controls. Methods. A total of 155 patients undergoing upper endoscopy were prospectively enrolled, including 50 with gastric cancer, 49 first-degree relatives of gastric cancer patients, and 56 controls. Serum concentrations of malondialdehyde (MDA) and glutathione) and activities of superoxide dismutase (SOD) and catalase were measured. Multivariate analysis adjusting for sex, age, smoking status, and alcohol consumption was performed. Results. Lipid peroxidation, as measured by concentration of MDA (nmol/mL), was higher ( p = 0.04 ), and glutathione levels were lower ( p < 0.001 ) in the gastric cancer group compared to controls. There was no difference in the catalase activity among the groups. There was no difference in glutathione and MDA concentration or catalase activity between the different stages of gastric cancer based on the TNM classification. Relatives of gastric cancer patients had higher glutathione concentration (μmol/mL) compared to gastric cancer patients (262.5 vs. 144.6; p = 0.018 ), while there was no difference in MDA concentration. Catalase and superoxide dismutase activity were lower in the gastric cancer group (3.82 vs. 0.91; p < 0.001 and 1.04 vs. 0.6; p < 0.001 ) compared to their first-degree relatives. Interestingly, MDA concentration in the first-degree relative group was higher than in the control group (7.9 vs. 5.1; p = 0.03 ). Conclusions. In this study, similarly to gastric cancer patients, their first-degree relatives were found to have increased oxidative stress compared to controls. Further studies are warranted to validate this observation and to better understand the role of oxidative stress as a possible biomarker in this population.

Study on the Characteristics of Intestinal Flora Composition in Gastric Cancer Patients and Healthy People in the Qinghai-Tibet Plateau

The aim of this study is to compare and analyze the structure and diversity of intestinal flora between gastric cancer patients and healthy people in the Qinghai-Tibet Plateau and to explore the characteristics of the intestinal flora composition in gastric cancer patients in the plateau area, and to determine the possible correlation between the intestinal flora and gastric cancer. Fresh feces from 22 cases of gastric cancer patients diagnosed in a tertiary hospital in Qinghai Province and 30 cases of healthy people during the same period were collected. The 52 subjects were undergone for 16S rDNA gene sequencing of intestinal bacteria to analyze and compare the diversity and compositional characteristics of intestinal flora. Analysis of the diversity of intestinal flora between the gastric cancer group and the healthy group was based on the Chao1 index of species richness, Shannon diversity index, and Simpson index. It showed that the gastric cancer group had no statistically difference from the healthy group (P > 0.05). In the Venn diagram, the number of OTU units shared by the gastric cancer group and the healthy group is 6997, and the number of unique OTU units in the healthy group is 2282, while the number of OTU units in the gastric cancer group is 896 and the difference is statistically significant (χ2 = 495.829), P < 0.000). Analysis of the composition and abundance distribution of intestinal flora showed that at the phylum level, there is no significant deference in abundance between the healthy group of Bacteroides and Firmicutes compared with the gastric cancer group (P > 0.05). However, there is a statistically significant difference in abundance between the healthy groups of Proteobacteria compared with the gastric cancer group (P < 0.05). At the genus level, the gastric cancer group of Prevotella_9 is significantly different from the healthy group (P < 0.05). Meanwhile, the gastric cancer group of Streptococcus and Lactobacillus are significantly different from the healthy group (P < 0.001). There are differences in the composition and abundance of intestinal flora between patients with gastric cancer and healthy people in plateau areas, suggesting that Proteobacteria, Prevotella_9, Streptococcus, and Lactobacillus have increased in the Qinghai-Tibet Plateau and becoming one of the factors related to the incidence of gastric cancer in the region.

Evidence of Epstein-Barr Virus Infection Association With Gastric Cancer and Gastroduodenal Diseases

Background: Epstein-Barr virus (EBV) is detected in epithelial tumors, such as nasopharyngeal carcinoma and gastric cancer (GC). EBV-associated gastric cancer is a distinct molecular subtype of gastrointestinal carcinomas as defined by Cancer Genome Atlas. This gamma-Herpes virus is present in approximately 10% of gastric carcinomas.Methods: The present study aimed to investigate the presence of EBV genome in gastric cancer and other gastroduodenal diseases either alone or together with Helicobacter pylori (HP). We examined 237 samples from Iranian patients diagnosed with GC and gastroduodenal disease for EBV infection by quantitative Real-Time PCR.Results: Of the 237 samples tested, EBV DNA was detected in 37 samples (15.6%), in 13 of the 81 GC cases (16%), and 24 of the 156 non-cancerous samples (15.4%). All samples containing EBV were gastric cancer of the intestinal type. Of 37 EBV-positive samples, 20 (54.1%) were over 55 years old and 20 (54.1%) were male. The EBV-EBER (EBV-encoded small RNA) DNA copy number in the gastric cancer group (mean = 2.14×10-1 copies/cell) was higher than that in the gastroduodenal disease group (mean = 1.39×10-2 copies/cell), and this difference was statistically significant (P> 0.001). Moreover, the concurrent infections with EBV and HP were detected in 17 out of 35 EBER-positive samples (48.6%), 6 (17/1%) cases were in the gastric cancer group and 11 (31/4%) cases were in the gastroduodenal disease group.Conclusions: In the present study, a high incidence (16%) of EBVaGC was observed in Babol city, Northern Iran. Also, the higher number of copies of EBV EBER DNA in the GC group than in the non-cancer group confirmed the possible role of EBV in inducing cancer. EBVaGC is not endemic in any region and varies in different nations. Therefore, further studies are needed to determine the role of this virus in the development of GC and other gastroduodenal diseases.

Expression and Clinical Significance of Serum Exosomal miR-375 in Patients with Gastric Cancer

To explore exosomal miR-375 expression in gastric cancer patients and its relationship with patient prognosis. A total of 53 patients diagnosed with gastric cancer in our hospital from May 2014 to May 2016 were included as the gastric cancer group, and 46 healthy women who came to our hospital for physical examination during the same period were enrolled as the healthy group. Exosomal miR-375 expression level was detected using qRT-PCR, and the diagnostic performance and prognostic significance of exosomal miR-375 in gastric cancer were explored. The gastric cancer group showed increased exosomal miR-375 expression than the healthy group (P< 0.05); Kaplan-Meier survival analysis exhibited that serum exosomal miR-375 has an AUC of 0.778, sensitivity of 69.57%, and specificity of 75.47%, whereas Cox regression analysis showed that the miR-375 expression in exosomes was an independent risk factor affecting the prognosis of gastric cancer patients (P< 0.05). Patient with gastric cancer showed upregulated miR-375 expression in serum exosomes. Serum exosomal miR-375 was found to has positive sensitivity and specificity in the diagnosis of gastric cancer, which may be associated with poor prognosis of gastric cancer patients.

Study on the Value of miR6503-5p Combined with PGR in the Diagnosis of Early Gastric Cancer

Objective To investigate the value of serum miRNA 6503-5p (miR6503-5p) combined with pepsinogen ratio (PGR) in the diagnosis of early gastric cancer. Methods: 94 patients (gastric cancer group) with gastric cancer confirmed by pathological examination and 90 patients with chronic atrophic gastritis collected by Department of Pathology in our hospital were selected as the control group, the serum levels of pepsinogen (PG I, PG II) and miR6503-5p were measured in the two groups, and the value of the two indexes in the diagnosis of gastric cancer was analyzed by ROC. Results: The serum levels of miR6503-5p in gastric cancer group were significantly higher than those in control group (P<0.05), the serum levels of PG I and PGR in gastric cancer group were significantly lower than those in control group (P<0.05), the serum levels of miR6503-5p in stage II gastric cancer group were significantly higher than those in stage I patients with statistically significant difference (P<0.05), and the serum levels of PG I and PGR in stage II gastric cancer group were significantly lower than those in stage I patients with statistically significant difference (P<0.05). The serum levels of PG I, PG II and PGR in the patients with highly and moderately differentiated gastric cancer were not significantly different from those in the patients with poorly and undifferentiated gastric cancer, with no statistically significant different (P>0.05); the serum levels of miR6503-5p in the patients with highly and moderately differentiated gastric cancer were significantly lower than those in the patients with poorly and undifferentiated gastric cancer, with statistically significant difference (P<0.05); the sensitivity of miR6503-5p in diagnosing gastric cancer was 81.33%, the specificity was 71.09%, the area under the ROC curve was 0.767; the sensitivity of PGR in diagnosing gastric cancer was 85.81%, the specificity was 78.40%, and the area under the ROC curve was 0.827. The sensitivity of serum miR6503-5p combined with PGR was 96.40%, the specificity was 85.44%, and the area under the ROC curve was 0.920. Conclusion The miR 6503-5p combined with PGR has high sensitivity and specificity in the diagnosis of gastric cancer and is worthy of clinical application in the screenof patient with early gastric cancer.

Diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PGII and CA199 in early gastric cancer

To explore the diagnostic value of MRI-DWI signal intensity value combined with serum PGI. PGII and CA199 in early gastric cancer. Sixty cases of gastric cancer patients admitted to our hospital from December 2019 to December 2020 were selected as the gastric cancer group and 80 cases of healthy volunteers who underwent physical examination in our hospital during the same period were selected as the healthy group. All the 60 patients underwent MRI-DWI examination, and the pathological diagnosis results were regarded as the gold standard. MRI-DWI images, MRI-DWI signal intensity values of patients with different degrees of gastric cancer differentiation. Serum PGI, PGII and CA199 levels of subjects in the two groups were compared. AUC was used to evaluate the diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PG II and CA199 for early gastric cancer. In the healthy group, T1W1 showed relatively uniform low signal intensity. While T2WI showed no significant increase in signal intensity. In the gastric cancer group. There was diffuse gastric wall thickening, local thickening or mass formation; T1WI and WATS showed slightly lower signal intensity in the lesion area. T2WI, FLAIR and B-TFE showed slightly uneven or moderately increased signal intensity. DWI showed limited diffusion, and the signal intensity increased uniformly or more uniformly, and the range of increase was clear. The signal intensity of MRI-DWI was 89.12 ± 8.14 in patients with low differentiation, 82.17 ± 6.35 in patients with moderate differentiation, and 74.52 ± 4.53 in patients with high differentiation. There were significant differences in the signal intensity of MRI-DWI among the three groups, and the difference was statistically significant (F=12.214, P <0.05). Serum PGI levels of subjects in the gastric cancer group were significantly lower than those in the healthy group, and the levels of PGII and CA199 were significantly higher than that in the healthy group, with statistical significance (P <0.05). The AUC, sensitivity and specificity of MRI-DWI signal intensity value and serum PGI, PGII and CA199 combined indexes in the diagnosis of gastric cancer were significantly higher than those of the independent indexes, with statistical significance (P <0.05). Conclusion: MRI-DWI signal strength value, serum PGI, PGII and CA199 levels are closely related to the occurrence and development of early gastric cancer. The combined detection and diagnosis efficiency is higher, which is helpful to improve the detection rate of early gastric cancer and is worthy of extensive clinical application.

Discovering Biomarkers in Gastric Cancer by Urine Metabolomics

IntroductionGastric cancer is one of the most common gastrointestinal tumors, ranking forth in incidence and second in mortality worldwide. Discovering molecular biomarkers for early gastric cancer diagnosis is of great importance. MethodsUrine and related clinical data of 40 patients with gastric cancer (20 in advanced stage and 20 in early stage) and 20 healthy volunteers from Jilin University First Hospital were collected. Liquid chromatography-mass spectrometry (LC-MS) was used to detect urine samples and the metabolic differences between the three groups of urine samples were analyzed. The principal component analysis was performed after data processing, and different metabolites were found using analysis of variance. Partial least square discriminant analysis was performed to further narrow the range of different metabolites. The precise mass to charge ratios of different metabolites were imported into the Human Metabolomics Database (HMDB). Finally, the identified different metabolites were further screened by cluster analysis and ROC curve. ResultsUrine samples of the healthy group (NOR), the early gastric cancer group (EGC), and the advanced gastric cancer group (AGC) were different metabolites. 324 statistically significant metabolites are screened out. The cluster analysis showed 7-Methylguanine, vinylacetylglycine, butyric acid, 4-Vinylphenol sulf, 5`-biotinyl-AMP, and 3-Amino-2-piperido in EGC, AGC and NGO were similar. 7-Methylguanine, vinylacetylglycine and 4-Vinylphenolsulfate had good diagnostic ability in EGC and NOR (p<0.05), and gastric cancer and NOR (p<0.05). ConclusionDifferences in the metabolites in urine between the early gastric cancer group and the healthy group were found. 7-Methylguanine, Vinylacetylglycine, and 4-Vinylphenolsulfate have good diagnostic ability and may be potential biomarkers of early gastric cancer.

Study on Blood Metabolomics of Early Gastric Cancer Based on Liquid Chromatography-Mass Spectrometry Technology

Background: Metabolomics is widely used to accurately find the basic characteristics and material basis of life activities. The purpose of this study is to use metabolomics to discover biomarkers for the diagnosis of early gastric cancer.Methods: We collected the blood samples and clinical data of 63 patients with gastric cancer from the First Hospital of Jilin University, including 26 patients with advanced gastric cancer (group A), 37 patients with early gastric cancer (group B), and 18 healthy volunteers (group C). Chromatography-mass spectrometry (LC-MS) is used for detect metabolites and obtain metabolic profile. Support vector machine (SVM) is used to screen the differential metabolites with a weight of 100% from the blood sample. Total ion current diagram, principal component analysis and analysis of variance (ANOVA) are used to identify differential metabolites. PCA and the quadratic discriminant analysis were used to evaluate the similarity between samples. The receiver characteristic curve (ROC) is used to evaluate the diagnostic ability of metabolites. After the nuclear ratio of the selected metabolites is imported into the Human Metabolome Database (HMDB), the structure is identified to determine the corresponding substances, and then the verification group is used to test the accuracy of the metabolites.Results: Through LC-MS, TIC, ANOVA and PCA, differential metabolites were found in different blood samples. Cluster analysis showed similar metabolites in the three groups A, B, and C. ROC curve represented the diagnostic ability of metabolites. The different metabolites between group A and C were spermine, enterostatin, heparin sulfate, and triacylglycerol. The difference metabolites between group A, group B and group C were same as those between group A and C. The cluster analysis and ROC also showed that all four metabolites had high specificity and sensitivity in the verification group. And the results of verification group were consistent with the experimental group.Conclusion: Spermine, enterostatin, heparin sulfate, and triacylglycerol may be potential biomarkers for the diagnosis of early gastric cancer.

The expression levels of miR-655-3p, miR127-5p, miR-369-3p, miR-544a in gastric cancer

Background Gastric cancer, one of the most common cancers in the world, is a multifactorial disease in which environmental and genetic factors play a role. In our study, we aimed to determine the expression levels of four miRNAs (miR127-5p, miR-544a, miR-369-3p and miR-655-3p) on chromosome 14q32 in gastric cancer. Materials and methods Total RNA was isolated from blood samples taken from 66 gastric cancer and 66 healthy individuals. The gene expression levels determined by cDNA and quantitative real-time polymerase chain reaction were analyzed according to the 2−∆∆Ct method. SPSS 22 were used for statistical analysis and p < 0.05 was considered as statistically significant. Results and discussion miR-655-3p (fold change: 100, p = 0.026), miR-127-5p (fold change: 48, p < 0.001) and miR-369-3p (fold change: 1.6, p > 0.05) was less expressed in the gastric cancer group than control group. miR-544a was found 15.5-fold more expressed in the patient group than control group (fold change: 15.47, p < 0.001). Conclusion miR127-5p, miR-544a, and miR-655-3p may be evaluated as biomarkers in gastric cancer.