Independent Risk Factors For Gastric Cancer Research Articles

Association between Gout and Gastric Cancer: A Nested Case-Control Study Using a National Health Sample Cohort.

Given the global significance of gout and gastric cancer (GC) as major health problems with interrelated impacts, we examined the development of GC in Korean patients with gout. We conducted a nested case-control study using data from 10,174 GC patients and 40,696 control patients from the Korean National Health Insurance Service-National Sample Cohort database. Propensity score matching (1:4) with propensity score overlap-weighted adjustment was used to reduce selection bias and estimate the odds ratio (OR) and 95% confidence intervals (CIs) for the association between gout and GC. An adjusted OR for GC was not significantly higher in patients with gout than in control patients (1.02; 95% CI, 0.93-1.12; p = 0.652). Additionally, no association between gout and GC was observed in subgroup analyses such as sex, age, level of income, region of residence, or Charlson Comorbidity Index score. In conclusion, these results suggest that gout is not a significant independent risk factor for GC among the Korean population. Additional investigation is required to establish a causal association between gout and GC, and to generalize these results to general populations.

Dose-response association between cigarette smoking and gastric cancer risk: a systematic review and meta-analysis.

This study aims at providing an accurate and up-to-date quantification of the dose-response association between cigarette smoking and gastric cancer (GC) risk, overall and by subsite. We conducted a systematic review and meta-analysis of case-control and cohort studies on the association between cigarette smoking and GC risk published up to January 2023. We estimated pooled relative risks (RR) of GC and its subsites according to smoking status, intensity, duration, and time since quitting. Among 271 eligible articles, 205 original studies were included in this meta-analysis. Compared with never smokers, the pooled RR for GC was 1.53 (95% confidence interval; CI 1.44-1.62; n = 92) for current and 1.30 (95% CI 1.23-1.37; n = 82) for former smokers. The RR for current compared with never smokers was 2.08 (95% CI 1.66-2.61; n = 21) for gastric cardia and 1.48 (95% CI 1.33-1.66; n = 8) for distal stomach cancer. GC risk nonlinearly increased with smoking intensity up to 20 cigarettes/day (RR:1.69; 95% CI 1.55-1.84) and levelled thereafter. GC risk significantly increased linearly with increasing smoking duration (RR: 1.31; 95% CI 1.25-1.37 for 20years) and significantly decreased linearly with increasing time since quitting (RR: 0.65; 95% CI 0.44-0.95 for 30years since cessation). The present meta-analysis confirms that cigarette smoking is an independent risk factor for GC, particularly for gastric cardia. GC risk increases with a low number of cigarettes up to 20 cigarettes/day and increases in a dose-dependent manner with smoking duration.

Diabetes Mellitus and Gastric Cancer: Correlation and Potential Mechanisms.

This review summarizes the correlation between diabetes mellitus (DM) and gastric cancer (GC) from the perspectives of epidemiology, drug use, and potential mechanisms. The association between DM and GC is inconclusive, and the positive direction of the association reported in most published meta-analyses suggests that DM may be an independent risk factor for GC. Many clinical investigations have shown that people with DM and GC who undergo gastrectomy may have better glycemic control. The potential link between DM and GC may involve the interaction of multiple common risk factors, such as obesity, hyperglycemia and hyperinsulinemia, H. pylori infection, and the use of metformin. Although in vitro and in vivo data support that H. pylori infection status and metformin can influence GC risk in DM patients, there are conflicting results. Patient survival outcomes are influenced by multiple factors, so further research is needed to identify the patients who may benefit.

Comparison of different risk stratifications for gastric cancer and establishing a simplified risk-scoring model based on the Kyoto classification.

The study aims to assess the value of different risk stratifications in diagnosing early gastric cancer (GC) and explore risk factors based on Kyoto gastritis classification. This study was a single-centered cross-sectional study; all epidemiological data and endoscopic findings were obtained prospectively. To evaluate the proportion of GC in each risk stratification and to compare the diagnostic performance of different methods using the receiver operating characteristic curve, univariable and multivariable analyses were used to explore the correlation between endoscopic findings and GC. A total of 240 subjects were enrolled, and the diagnostic efficacy of the Kyoto Classification Score was similar to Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stage, and the accuracy was higher than that of the Japanese scoring system and OLGA stage. Moderate atrophy (odds ratio [OR]=3.52, 95% confidence interval [CI]: 1.52-8.16), severe atrophy (OR=4.96, 95% CI: 1.75-14.04), map-like redness (OR=9.89, 95% CI: 1.16-84.15), and xanthelasma (OR=3.57, 95% CI: 1.15-11.15) were independent risk factors for GC. The simplified Kyoto classification (area under the receiver operating characteristic [AUROC]=0.76, P=0.58) based on multivariable analysis demonstrated favorable diagnostic value compared with traditional Kyoto classification score (AUROC=0.74). This study confirms the value of the Kyoto classification score and the OLGIM stage in the risk stratification of GC. Simplified Kyoto classification is also promising in risk assessment of GC but still requires validation in the population.

Integrated multi-dimensional analysis highlights DHCR7 mutations involving in cholesterol biosynthesis and contributing therapy of gastric cancer

BackgroundGenetic background plays an important role in the occurrence and development of gastric cancer (GC). With the application of genome-wide association study (GWAS), an increasing number of tumor susceptibility genes in gastric cancer have been discovered. While little of them can be further applicated in clinical diagnosis and treatment due to the lack of in-depth analysis.MethodsA GWAS of peripheral blood leukocytes from GC patients was performed to identify and obtain genetic background data. In combination with a clinical investigation, key SNP mutations and mutated genes were screened. Via in vitro and in vivo experiments, the function of the mutated gene was verified in GC. Via a combination of molecular function studies and amino acid network analysis, co-mutations were discovered and further identified as potential therapeutic targets.ResultsAt the genetic level, the G allele of rs104886038 in DHCR7 was a protective factor identified by the GWAS. Clinical investigation showed that patients with the rs104886038 A/G genotype, age ≥ 60, smoking ≥ 10 cigarettes/day, heavy drinking and H. pylori infection were independent risk factors for GC, with odds ratios of 12.33 (95% CI, 2.10 ~ 72.54), 20.42 (95% CI, 2.46 ~ 169.83), and 11.39 (95% CI, 1.82 ~ 71.21), respectively. Then molecular function studies indicated that DHCR7 regulated cell proliferation, migration, and invasion as well as apoptosis resistance via cellular cholesterol biosynthesis pathway. Further amino acid network analysis based on the predicted structure of DHCR7 and experimental verification indicated that rs104886035 and rs104886038 co-mutation reduced the stability of DHCR7 and induced its degradation. DHCR7 mutation suppressed the malignant behaviour of GC cells and induced apoptosis via inhibition on cell cholesterol biosynthesis.ConclusionIn this work, we provided a comprehensive multi-dimensional analysis strategy which can be applied to in-depth exploration of GWAS data. DHCR7 and its mutation sites identified by this strategy are potential theratic targets of GC via inhibition of cholesterol biosynthesis.

Dickkopf-related protein 1/cytoskeleton-associated protein 4 signaling activation by Helicobacter pylori-induced activator protein-1 promotes gastric tumorigenesis via the PI3K/AKT/mTOR pathway

Gastric cancer (GC) is a common malignant tumor with high incidence and mortality rates globally, especially in East Asian countries. Helicobacter pylori (H. pylori) infection is a significant and independent risk factor for GC. However, its underlying mechanism of action is not fully understood. Dickkopf-related protein (DKK) 1 is a Wnt signaling antagonist, and cytoskeleton-associated protein (CKAP) 4 is a newly identified DKK1 receptor. Recent studies found that the binding of DKK1 to CAKP4 mediated the procancer signaling of DKK1 inde-pendent of Wnt signaling. We hypothesize that H. pylori-induced activation of DKK1/CKAP4 signaling contributes to the initiation and progression of GC. To investigate the interaction of H. pylori infection, DKK1 and CAKP4 in GC, as well as the underlying molecular mechanisms. RNA sequencing was used to identify differentially expressed genes (DEGs) between H. pylori-infected and uninfected primary GC cells. Gain- and loss-of-function experiments were performed to verify the H. pylori-induced upregulation of activator protein-1 (AP-1) in GC cells. A dual-luciferase reporter assay and co-immunoprecipitation were used to determine the binding of AP-1 to the DKK1 promoter and DKK1 to CKAP4. Western blotting and immunohistochemistry detected the expression of DKK1, CKAP4, and phos-phatidylinositol 3-kinase (PI3K) pathway-related proteins in GC cells and tissues. Functional experiments and tumorigenicity in nude mice detected malignant behavior of GC cells in vitro and in vivo. We identified 32 DEGs between primary GC cells with and without H. pylori infection, including JUN, fos-like antigen-1 (FOSL1), and DKK1, and confirmed that the three proteins and CKAP4 were highly expressed in H. pylori-infected GC cells, H. pylori-infected gerbil gastric tissues, and human GC tissues. JUN and FOSL1 form AP-1 to transcriptionally activate DKK1 expression by binding to the DKK1 promoter. Activated DKK1 bound to CKAP4, but not the most common Wnt coreceptor low-density lipoprotein receptor-related protein 5/6, to promote GC cell growth, colony formation, migration, invasion, and xenograft tumor growth in nude mice. All these effects were driven by activation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. Targeting the PI3K signaling pathway by LY294002 inhibited DKK1-mediated CKAP4/PI3K signaling activity and the malignant behavior of GC cells. H. pylori induces JUN and FOSL1 expression to form AP-1, which transcriptionally activates DKK1. Binding of DKK1 to KAKP4 contributes to gastric tumorigenesis via the PI3K/AKT/mTOR pathway.

Aberrant Expression TFR1/CD71 in Gastric Cancer Identifies a Novel Potential Prognostic Marker and Therapeutic Target.

Background Gastric cancer (GC) is one of the most common malignant tumors with poor prognosis. So far, other than the HER2, GC lacks effective therapeutic targets. Transferrin receptor 1 (TFR1) expressions are abnormally upregulated in various cancers for the satisfaction of iron demand increased. This study aimed to explore the expression and clinical value of TFR1 in GC. Methods A tissue microarray including GC tissues and matched noncancerous tissues from 155 GC patients were collected. Moreover, the level of TFR1 expression was detected by immunohistochemistry, and we also evaluated the relationship between TFR1 expression and the clinicopathologic characteristics. What is more, univariate analysis and multivariate analysis were used to evaluate the risk factors and independent risk factors affecting the prognosis of GC. Results We found that TFR1 was overexpressed in GC tissues compared with noncancerous tissues, and a significant relationship was found between TFR1 expression and age (P=0.001), Lauren type (P=0.008), T stage (P=0.003), HER2 (P=0.003), PD-L1 (P < 0.001), and the level of CA72-4 (P=0.028). Survival analysis confirmed that GC patients with positive TFR1 expression had a poorer OS than that with negative TFR1 expression, and TFR1 expression was an independent risk factor in GC. Furthermore, we also found that there was a significant difference between the TFR1-PD-L1− group and the TFR1+PD-L1+ group (P=0.023), while there was no significant difference between the TFR1-PD-L1− group and the TFR1+PD-L1− group (P=0.119), or between the TFR1-PD-L1− group and the TFR1-PD-L1+ group (P=0.396). Conclusions TFR1 was overexpressed in GC and its aberrant expression identifies a novel potential prognostic marker and therapeutic target. In addition, TFR1 expression may be associated with the immune microenvironment and suppress the immune response via regulating the PD-L1 expression.

Combination of Serum Test and Questionnaire in Early Gastric Cancer Screening.

Background:We aimed to analyze the predictive role of serum test and questionnaire in Early Gastric Cancer in The First Affiliated Hospital of Xingtai Medical College, Hebei Province from 2019 to 2020.Methods:In this prospective study, 280 medical examiners underwent questionnaire, serum test and gastroscopy. They were divided into Gastric cancer (GC) and Non-Gastric cancer (NGC) group. NGC group was divided into Low-grade intraepithelial neoplasia (LGIN), Chronic atrophic gastritis (CAG) and Non-chronic atrophic gastritis (NCAG) group.Results:Age, drinking, sex and Gastrin-17(G-17) was respectively independent risk factors for GC. Age, drinking and G-17 was independent risk factors for GC in men. G-17 of GC group was higher than that of LGIN and NCAG group (P<0.05). Pepsinogen I/II ratio (PGR) of GC was lower than that of NCAG group (P<0.05). There was no significant difference between Pepsinogen I (PGI) and Pepsinogen II (PGII) in the four groups. Helicobacter pylori-immunoglobulin G antibodies (H. pylori-IgG) of LGIN group was significantly higher than that of CAG and NCAG group in gastritis group (P<0.008). G-17≥42.95 pmol/L, age≥69years, male and drinking can predict GC.Conclusion:Older, drinking, men and high G-17 could respectively predict GC. Especially in men, older, drinking and high G-17 could affect the occurrence of GC. G-17, age, drinking and sex used respectively to screen high-risk populations for GC were more efficient than combined screening. GC had a higher serum G-17 and a lower PG than other gastric diseases.

Stemness-related LncRNA pair signature for predicting therapy response in gastric cancer

ObjectiveAs a critical feature of cancers, stemness is acknowledged as a contributor to the development of drug resistance in gastric cancer (GC). LncRNAs have been revealed to participate in this process. In this study, we tried to develop a stemness-related lncRNA pair signature as guidance for clinical decisions.MethodsThe analysis was initiated by collecting stemness-related lncRNAs in TCGA cohort. The differentially expressed stemness-related lncRNAs between normal and tumor tissues in GC patients from TCGA datasets were further collected to establish the signature based on Lasso and Cox regression analyses. The predictive efficacy of the signature for chemotherapy and immunotherapy was also tested. The practicality of this signature was also validated by Zhongshan cohort.ResultsA 13-DEsrlncRNA pair-based signature was established. The cutoff point acquired by the AIC algorithm divided the TCGA cohort into high and low risk groups. We found that the low-risk group presented with better survival (Kaplan-Meier analysis, p < 0.001). Cox regression analyse was also conducted to confirm the signature as an independent risk factor for GC {p < 0.001, HR = 1.300, 95% CI (1.231–1.373)]}. As for the practicality of this signature, the IC50 of cytotoxic chemotherapeutics was significantly higher in the high-risk group. The low-risk group also presented with higher immunophenoscore (IPS) in both the “CTLA4+ PD1+” (Mann-Whitney U test, p = 0.019) and “CTLA4- PD1+” (Mann-Whitney U test, p = 0.013) groups, indicating higher sensitivity to immunotherapy. The efficacy of the signature was also validated by Zhongshan cohort.ConclusionsThis study could not only provide a stemness-related lncRNA signature for survival prediction in GC patients but also established a model with predictive potentials for GC patients’ sensitivity to chemotherapy and immunotherapy.

Weighted correlation network analysis identifies FN1, COL1A1 and SERPINE1 associated with the progression and prognosis of gastric cancer.

Gastric cancer (GC) is one of the most deadliest tumours worldwide, and its prognosis remains poor. This study aims to identify and validate hub genes associated with the progression and prognosis of GC by constructing a weighted correlation network. The gene co-expression network was constructed by the WGCNA package based on GC samples and clinical data from the TCGA database. The module of interest that was highly related to clinical traits, including stage, grade and overall survival (OS), was identified. GO and KEGG pathway enrichment analyses were performed using the clusterprofiler package in R. Cytoscape software was used to identify the 10 hub genes. Differential expression and survival analyses were performed on GEPIA web resources and verified by four GEO datasets and our clinical gastric specimens. The receiver operating characteristic (ROC) curves of hub genes were plotted using the pROC package in R. The potential pathogenic mechanisms of hub genes were analysed using gene set enrichment analysis (GSEA) software. A total of ten modules were detected, and the magenta module was identified as highly related to OS, stage and grade. Enrichment analysis of magenta module indicated that ECM-receptor interaction, focal adhesion, PI3K-Akt pathway, proteoglycans in cancer were significantly enriched. The PPI network identified ten hub genes, namely COL1A1, COL1A2, FN1, POSTN, THBS2, COL11A1, SPP1, MMP13, COMP, and SERPINE1. Three hub genes (FN1, COL1A1 and SERPINE1) were finally identified to be associated with carcinogenicity and poor prognosis of GC, and all were independent risk factors for GC. The area under the curve (AUC) values of FN1, COL1A1 and SERPINE1 for the prediction of GC were 0.702, 0.917 and 0.812, respectively. GSEA showed that three hub genes share 15 common upregulated biological pathways, including hypoxia, epithelial mesenchymal transition, angiogenesis, and apoptosis. We identified FN1, COL1A1 and SERPINE1 as being associated with the progression and poor prognosis of GC.

Molecular Subtypes and CD4+ Memory T Cell-Based Signature Associated With Clinical Outcomes in Gastric Cancer.

BackgroundCD4+ memory T cells are an important component of the tumor microenvironment (TME) and affect tumor occurrence and progression. Nevertheless, there has been no systematic analysis of the effect of CD4+ memory T cells in gastric cancer (GC).MethodsThree datasets obtained from microarray and the corresponding clinical data of GC patients were retrieved and downloaded from the Gene Expression Omnibus (GEO) database. We uploaded the normalize gene expression data with standard annotation to the CIBERSORT web portal for evaluating the proportion of immune cells in the GC samples. The WGCNA was performed to identify the modules the CD4+ memory T cell related module (CD4+ MTRM) which was most significantly associated with CD4+ memory T cell. Univariate Cox analysis was used to screen prognostic CD4+ memory T cell-related genes (CD4+ MTRGs) in CD4+ MTRM. LASSO analysis and multivariate Cox analysis were then performed to construct a prognostic gene signature whose effect was evaluated by Kaplan-Meier curves and receiver operating characteristic (ROC), Harrell’s concordance index (C-index), and decision curve analyses (DCA). A prognostic nomogram was finally established based on the CD4+ MTRGs.ResultWe observed that a high abundance of CD4+ memory T cells was associated with better survival in GC patients. CD4+ MTRM was used to stratify GC patients into three clusters by unsupervised clustering analysis and ten CD4+ MTRGs were identified. Overall survival, five immune checkpoint genes and 17 types of immunocytes were observed to be significantly different among the three clusters. A ten-CD4+ MTRG signature was constructed to predict GC patient prognosis. The ten-CD4+ MTRG signature could divide GC patients into high- and low-risk groups with distinct OS rates. Multivariate Cox analysis suggested that the ten-CD4+ MTRG signature was an independent risk factor in GC. A nomogram incorporating this signature and clinical variables was established, and the C-index was 0.73 (95% CI: 0.697–0.763). Calibration curves and DCA presented high credibility for the OS nomogram.ConclusionWe identified three molecule subtypes, ten CD4+ MTRGs, and generated a prognostic nomogram that reliably predicts OS in GC. These findings have implications for precise prognosis prediction and individualized targeted therapy.

Increased IGFBP7 Expression Correlates with Poor Prognosis and Immune Infiltration in Gastric Cancer.

Background: Insulin-like growth factor binding protein-7 (IGFBP7) contributes to multiple biological processes in various tumors. However, the role of IGFBP7 in gastric cancer (GC) is still undetermined. The study aims to explore the role of IGFBP7 in GC via an integrated bioinformatics analysis.Methods: IGFBP7 expression levels in GC and its normal gastric tissues were analyzed using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, as well as by our clinical gastric specimens. The methylation analysis was conducted with MEXPRESS, UALCAN and Xena online tools. The survival analysis was conducted using the Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Coexpressed genes of IGFBP7 were selected with the cBioPortal tool and enrichment analysis was conducted with the clusterProfiler package in R software. Gene set enrichment analysis (GSEA) was performed to explore the IGFBP7-related biological processes involved in GC. Correlations between IGFBP7 and immune cell infiltrates were analyzed using the TIMER database.Results: IGFBP7 expression was significantly upregulated in GC and correlated with stage, grade, tumor status and Helicobacter pylori infection. High IGFBP7 expression and low IGFBP7 methylation levels were significantly associated with short survival of patients with GC. Univariate and multivariate analyses revealed that IGFBP7 was an independent risk factor for GC. The coexpressed genes LHFPL6, SEPTIN4, HSPB2, LAYN and GGT5 predicted unfavorable outcomes of GC. Enrichment analysis showed that the coexpressed genes were involved in extracellular matrix (ECM)-related processes. GSEA indicated that IGFBP7 was positively related to ECM and inflammation-related pathways. TIMER analysis indicated that the mRNA level of IGFBP7 was strongly correlated with genes related to various infiltrating immune cells in GC, especially with gene markers of tumor associated macrophages (TAMs).Conclusions: Increased IGFBP7 expression correlates with poor prognosis and immune cell infiltration in GC, which might be a potential biomarker for the diagnosis of GC.

Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders

BACKGROUNDPolymorphisms of human leukocyte antigen (HLA) genes are suggested to increase the risk of gastric cancer (GC).AIMTo investigate the HLA allele frequencies of patients with GC relative to a control group in terms of CagA+ multiple (≥ 2) EPIYA-C repeats.METHODSThe patient group comprised 94 patients [44 GC and 50 duodenal ulcer (DU) patients], and the control group comprised 86 individuals [(50 non-ulcer dyspepsia patients and 36 people with asymptomatic Helicobacter pylori (H. pylori)]. Polymerase chain reaction was performed for the amplification of the H. pylori cagA gene and typing of EPIYA motifs. HLA sequence-specific oligonucleotide (SSO) typing was performed using Lifecodes SSO typing kits (HLA-A, HLA-B HLA-C, HLA-DRB1, and HLA-DQA1-B1 kits).RESULTSThe comparison of GC cases in terms of CagA+ multiple (≥ 2) EPIYA-C repeats showed that only the HLA-DQB1*06 allele [odds ratio (OR): 0.37, P = 0.036] was significantly lower, but significance was lost after correction (Pc = 0.1845). The HLA-DQA1*01 allele had a high ratio in GC cases with multiple EPIYA-C repeats, but this was not significant in the univariate analysis. We compared allele frequencies in the DU cases alone and in GC and DU cases together using the same criterion, and none of the HLA alleles were significantly associated with GC or DU. Also, none of the alleles were detected as independent risk factors after the multivariate analysis. On the other hand, in a multivariate logistic regression with no discriminative criterion, HLA-DQA1*01 (OR = 1.848), HLA-DQB1*06 (OR = 1.821) and HLA-A*02 (OR = 1.579) alleles were detected as independent risk factors for GC and DU.CONCLUSIONNone of the HLA alleles were detected as independent risk factors in terms of CagA+ multiple EPIYA-C repeats. However, HLA-DQA1*01, HLA-DQB1*0601, and HLA-A*2 were independent risk factors with no criterion in the multivariate analysis. We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.

Up-regulation of long noncoding RNA LINC00858 is associated with poor prognosis in gastric cancer.

The present study aimed to investigated the expression pattern of long noncoding RNA LINC00858 (LINC00858) in gastric cancer (GC) patients and its feasibility as a new prognostic biomarker. We examined LINC00858 expression in GC tissues and matched normal tissues from 189 patients using a quantitative reverse transcription-polymerase chain reaction. The correlations of LINC00858 levels in GC patients with clinicopathologic features were analyzed using a chi-squared test. The influence of LINC00858 on the overall survival rate of GC patients was precisely calculated using Kaplan-Meier methods (log rank tests). Multivariate Cox regression assays were carried out for the identification of the independent risk factors for GC. We observed that LINC00858 was distinctly up-regulated in GC tissues compared to adjacent non-tumor specimens (p < 0.01). Higher expression of LINC00858 in GC was found to be associated with TNM stage (p = 0.003) and lymphatic metastasis (p = 0.007). Using Kaplan-Meier assays, we found that patients with high expression levels of LINC00858 had a distinctly poor overall survival and disease-free survival compared to those with low expression levels of LINC00858 (p = 0.0102). Multivariate analyses confirmed that LINC00858 (p < 0.05) was an independent prognosis factor for GC patients. The data obtained in our study indicate that LINC00858 may be used as a novel prognostic indicator in GC patients.

Low expression of lncRNA MGC27345 is associated with poor prognosis in gastric cancer patients.

A series of evidence showed that long non-coding RNAs (lncRNAs) play an essential regulatory role in the occurrence and development of human cancer, and is a potential biological target in the fight against cancer. In this research, we investigated the role of lncRNA MGC27345 in gastric cancer (GC), the expression of MGC27345 in GC was detected by quantitative Real-Time PCR in GC tissue from 235 patients. The correlations between MGC27345 expression and clinicopathological variables and survival were evaluated by the Chi-square test. Kaplan-Meier method (log-rank test), univariate and multivariate Cox regression assays were carried out for the identification of the survival and independent risk factors for GC. MGC27345 expression levels were significantly decreased in GC tissues than in adjacent normal specimens. Lower expression of MGC27345 was found in advanced tumor stages. GC patients with low-expression of MGC27345 had a poorer overall survival compare to those with high-expression of MGC27345. Furthermore, MGC27345 was an independent protective prognosis factor in GC development. Our data indicated that MGC27345 may have a diagnostic and prognostic value for patients with advanced gastric cancer and assist to improve clinical outcomes for GC patients.

Clinical Significance of Serum CA125, CA19-9, CA72-4, and Fibrinogen-to-Lymphocyte Ratio in Gastric Cancer With Peritoneal Dissemination.

Background: Relevant serum tumor markers have been indicated to be associated with peritoneal dissemination (PD) of gastric cancer (GC). Fibrinogen has been shown to play an important role in the systemic inflammatory response (SIR) and in tumor progression. However, the clinical significance of the fibrinogen-to-lymphocyte ratio (FLR) in GC with PD has not been studied.Methods: The clinical data of 391 patients with GC were collected, including 86 cases of PD. Then, 1:3 matching was performed by propensity score matching (PSM), and the clinical data of the matched 344 patients were analyzed by univariate and multivariate conditional logistic regression. Classification tree analysis was used to obtain the decision rules and a random forest algorithm to extract the important risk factors of PD in GC. A nomogram model for risk assessment of PD in GC was established by using the rms package of R software.Results: Univariate analysis showed that the factors related to PD in GC were: carbohydrate antigen (CA) 125 (P < 0.0001), CA19-9 (P < 0.0001), CA72-4 (P < 0.0001), FLR (P < 0.0001), neutrophil-to-lymphocyte ratio (NLR) (P < 0.0001), albumin-to- lymphocyte ratio (ALR) (P < 0.0001), platelet-to-lymphocyte ratio (PLR) (P = 0.013), and carcinoembryonic antigen (CEA) (P = 0.031). Conditional logistic regression found that CA125 (OR: 1.046; P < 0.0001), CA19-9 (OR: 1.002; P < 0.0001), and FLR (OR: 1.266; P = 0.024) were independent risk factors for GC with PD. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the decision rules for detecting PD of GC were 89.5, 77.4, 94.0, 82.8, and 91.8%, respectively. According to the important variables identified by the classification tree and random forest algorithm, the risk assessment model of PD in GC was established. The accuracy, sensitivity, and specificity of the model were 91, 89.5, and 79.5%, respectively.Conclusion: CA125 > 17.3 U/ml, CA19-9 > 27.315 U/ml, and FLR > 2.555 were the risk factors for GC with PD. The decision rules and nomogram model constructed by CA125, CA19-9, CA72-4, and FLR can correctly predict the risk of PD in GC.

ILF3 promotes gastric cancer proliferation and may be used as a prognostic marker.

Interleukin enhancer-binding factor 3 (ILF3) may function as a transcriptional coactivator and has been reported to be involved in tumor proliferation and metastasis; however, its role and clinical value in gastric cancer (GC) remains unclear. To understand the value of ILF3 in GC, a total of 80 matched samples selected from GC tissues and the adjacent mucosa were used to evaluate the expression of ILF3 and its association with clinical characteristics. Furthermore, its biological functions and mechanisms were investigated using SGC-7901 and BGC823 cell lines. Immunohistochemistry demonstrated that the positive expression rates of ILF3 in GC tissue were higher compared with those in adjacent mucosa (P<0.05). Significantly overexpressed ILF3 was detected in BGC823 and SGC7901 cells, and the MTT results demonstrated decreased cell activity after ILF3 expression was inhibited. The proportions of cells in the G0/G1 phase increased, while the number of cells in the G2/M phase decreased, and the expression of the genes associated with proliferation varied following inhibition of ILF3 (P<0.05). Positive expression of ILF3 was associated with a poor prognosis for patients with GC, and was an independent risk factor for GC (P<0.05). In conclusion, ILF3 is involved in the deterioration of GC by promoting proliferation of GC cells, and ILF3 protein detection may assist in the prediction of the prognosis of patients with GC.

Circ_0009910 regulates growth and metastasis and is associated with poor prognosis in gastric cancer.

Circular RNAs (circRNAs) have recently shown capabilities as gene regulators in mammals. In this study, we aimed to evaluate the effects and mechanism of circ_0009910 in gastric cancer (GC). Circ_0009910 expression was quantified by Real-time PCR in human GC cell lines and tissues. Association between circ_0009910 levels and clinicopathological factors and patient's prognosis was analyzed. The roles of circ_0009910 in regulating GC cell proliferation, colony formation, migration, and invasion were evaluated in vitro. Western blot analysis was conducted to detect the expressions of molecular markers of epithelial-mesenchymal transition (EMT). Circ_0009910 expression level was elevated in GC tissues and cell lines and associated with clinical stage (p = 0.032), distant metastasis (p = 0.028) and differentiation (p = 0.007). Kaplan-Meier survival analysis indicated that circ_0009910 expression in positive group has a worse overall survival compared to the negative group (p = 0.0013). Multivariate analysis showed that circ_0009910 was an independent risk factor for GC (HR = 2.346, 95% CI: 1.673-3.775, p = 0.006). Knockdown of circ_0009910 expression can suppress BGC823 and AGS cells proliferation, migration and invasion in vitro experiments. The results of Western blot indicated that knockdown of circ_0009910 increased expression of E-cadherin and decreased expression of the mesenchymal markers, snail and N-cadherin. Altogether, we demonstrate that circ_0009910 acts as a prognostic biomarker and promote cell proliferation, migration, invasion and EMT in GC, indicating that circ_0009910 may be a novel potential biomarker and therapeutic target of GC.

Metformin Use and Gastric Cancer Risk in Diabetic Patients After Helicobacter pylori Eradication.

Although prior studies showed metformin could reduce gastric cancer (GC) risk in patients with diabetes mellitus, they failed to adjust for Helicobacter pylori infection and glycemic control. We aimed to investigate whether metformin reduced GC risk in H. pylori-eradicated diabetic patients and its association with glycemic control. This was a territory-wide cohort study using hospital registry database, recruiting all diabetic patients who were prescribed clarithromycin-based triple therapy for H. pylori infection from 2003 to 2012. Subjects were observed from H. pylori therapy prescription until GC diagnosis, death, or end of study (December 2015). Exclusion criteria included GC diagnosed within first year of H. pylori therapy, prior history of GC or gastrectomy, and failure of H. pylori eradication. The hazard ratio (HR) of GC with metformin (defined as at least 180-day use) was estimated by Cox model with propensity score adjustment for covariates (age, sex, comorbidities, medications [including insulin], and time-weighted average hemoglobin A1c [HbA1c]). All statistical tests were two-sided. During a median follow-up of 7.1 years (IQR = 4.7-9.8), 37 (0.51%) of 7266 diabetic patients developed GC at a median age of 76.4 years (IQR = 64.8-81.5 years). Metformin use was associated with a reduced GC risk (adjusted HR = 0.49, 95% CI = 0.24 to 0.98). There was a trend towards a lower GC risk with increasing duration (Ptrend = .01) and dose of metformin (Ptrend = .02). HbA1c level was not an independent risk factor for GC. Metformin use was associated with a lower GC risk among H. pylori-eradicated diabetic patients in a duration- and dose-response manner, which was independent of HbA1c level.

Usefulness of OLGA and OLGIM system not only for intestinal type but also for diffuse type of gastric cancer, and no interaction among the gastric cancer risk factors.

The operative link on gastric atrophy (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) stages have been suggested for risk estimation of gastric cancer (GC). However, usefulness of OLGA/OLGIM systems in diffuse type of GC was not investigated so far. The aims of this study were to evaluate the OLGA/OLGIM systems in estimating the GC risk according to Lauren's classification and to investigate the interaction among the risk factors. The OLGA/OLGIM stages were evaluated in 1398 (765 control and 633 GC patients) who were prospectively enrolled in the Seoul National University Bundang Hospital. Synergistic interaction among the risk factors for GC was calculated using an additive model. Among 387 intestinal-type GC patients, 71 (18.3%) were high-risk OLGA stages (III, IV) and 113 (29.2%) were high-risk OLGIM stages (III, IV). Of the 246 patients with diffuse-type GC, 36 (14.6%) were high-risk OLGA stages and 39 (15.9%) were high-risk OLGIM stages. Multivariable analysis revealed family history of GC, Helicobacter pylori infection, high-risk OLGA stages, and high-risk OLGIM stages as independent risk factors for GC regardless of histologic type (odds ratios [ORs] 1.78, 1.94, 2.63, and 3.18, respectively). There was no significant risk modification among the H. pylori infection, family history of GC, and high-risk OLGA/OLGIM stages. High-risk OLGA/OLGIM stages are important prediction markers for GC regardless of H. pylori infection or family history of GC not only for the intestinal type but also for diffuse-type GC.