Clinical pathological characteristics of“crawling-type”gastric adenocarcinoma cancer:A case report

BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.

Role of savolitinib in advanced gastric adenocarcinoma with meningeal carcinomatosis and cerebellar metastasis:A case report

BACKGROUND Brain metastases(BM)are very rare in gastric adenocarcinoma(GaC),and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness.However,its pathogenesis remains unclear.Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor(MET)amplification.Therefore,treatment with savolitinib,a small molecule inhibitor of c-Met,was selected.CASE SUMMARY A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain.Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy.The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department.Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification.After discussing treatment options with the patient,savolitinib tablets were administered.After a month of treatment,the intracranial lesions shrank considerably.CONCLUSION BM is very rare in advanced GaC,especially in meningeal cancer,that is characterized by rapid disease deterioration.There are very few effective treatment options available;however,technological breakthroughs in genomics have provided a basis for personalized treatment.Furthermore,MET amplification may be a key driver of BM in gastric cancer;however,this conclusion requires further investigation.

Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus

BACKGROUND Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus(RGAVCT)have a poor prognosis,with a 5-year survival rate ranging from 18.42%-53.57%.These patients need a reasonable postoperative treatment plan to improve their prognosis.AIM To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT.METHODS We retrospectively collected the clinicopathological data of 530 patients who un-derwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus.Fur-thermore,we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by asse-ssing the clinical and pathological features of the patients who met the inclusion criteria.We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses.The subgroups of pa-tients with stages Ⅰ,Ⅱ,and Ⅲ disease who received single-,dual-,or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0.RESULTS In all,530 eligible individuals with RGAVCT were enrolled in this study.The median overall survival(OS)of patients with RGAVCT was 24 months,and the survival rates were 80.2%,62.5%,and 42.3%at 12,24,and 59 months,respectively.Preoperative complications,tumor size,T stage,and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model.A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage Ⅰ or Ⅱ RGAVCT;however,chemotherapy did have an effect on OS of stage Ⅲ patients.Stage Ⅲ patients who were treated with chemotherapy consisting of dual-or triple-agent regimens had better survival than those treated with single-agent regimens,and no significant difference was observed in the survival of patients treated with chemo-therapy consisting of dual-or triple-agent regimens.CONCLUSION For patients with stage Ⅲ RGAVCT,a dual-agent regimen of postoperative chemotherapy should be recom-mended rather than a triple-agent treatment,as the latter is associated with increased frequency of adverse events.

Prognostic value of claudin 18.2 expression in gastric adenocarcinoma

BACKGROUND Claudin 18.2(CLDN18.2)is a cell surface protein expressed by gastric cancer cells.The monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death.A few studies researched the prognostic effect of CLDN18.2 expression in metastatic gastric adenocarcinoma.AIM To identify the prognostic value of CLDN18.2 expression in patients with metastatic gastric adenocarcinoma.METHODS This study was conducted with 65 patients over the age of 18 who were diagnosed with metastatic gastric adenocarcinoma.We investigated the effect of CLDN18.2 expression on clinicopathological characteristics(age,sex,histological grade,Lauren classification,family history,metastatic site,HER2 expression)and prognosis for patients with metastatic gastric adenocarcinoma.RESULTS CLDN18.2 expression was positive in 73.8%(48)of the patients.During the median 17.7-mo follow-up period,89.2%(58)of the patients died.Median progression-free survival and overall survival(OS)were 6 mo(95%confidence interval:1.6-10.4)and 12 mo(95%confidence interval:7.5-16.5).There was no statistically significant correlation between CLDN18.2 expression and clinicopathological characteristics of the patients.In univariate and multivariate Cox regression analysis,there was no correlation between clinicopathological characteristics of patients and progression-free survival or OS.CONCLUSION CLDN18.2 expression was quite high in patients with gastric adenocarcinoma,identifying the proportion of the patients in whom zolbetuximab would be efficacious.There is no statistically significant correlation with clinicopathological characteristics and OS.CLDN18.2 is not a prognostic marker in patients with gastric adenocarcinoma,although it is predictive.

Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase Ⅱ clinical trial

Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric cancer.This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)patients.Methods:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line chemotherapy.The primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and safety.Results:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,respectively.Grade 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of patients.Frequent grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.

Role of pre-existing incomplete intestinal metaplasia in gastric adenocarcinoma:A retrospective case series analysis

BACKGROUND Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial.AIM To analysis of patients having developed gastric adenocarcinoma during the period of follow-up.METHODS We conducted a retrospective study on patients having undergone upper endoscopy prior to the development of gastric adenocarcinoma. The presence and stage of precancerous lesions as well as subtype of intestinal metaplasia at the baseline endoscopy got evaluated. Literature mini-review was performed.RESULTS Out of 1681 subjects in the Biobank, gastric adenocarcinoma was detected in five cases in whom previous endoscopy data with biopsies either from the corpus or antral part were available. All of the patients had incomplete intestinal metaplasia during the baseline endoscopy;all three subjects in whom intestinal metaplasia subtyping was performed according to Filipe et al, had Type Ⅲ intestinal metaplasia. Two of the five cases had low Operative Link on Gastritis Assessment(OLGA) and Operative Link on Gastritis Intestinal Metaplasia Assessment(OLGIM) stages(Ⅰ-Ⅱ) at the baseline.CONCLUSION The presence of incomplete intestinal metaplasia, in particular, that of Type Ⅲ is a better predictor for gastric adenocarcinoma development than OLGA/OLGIM staging system. Subtyping of intestinal metaplasia have an important role in the risk stratification for surveillance decisions.

Effects of JAG-1 on the Proliferation and Migration of Gastric Adenocarcinoma Cells after TRAIP Knockout

[Objectives]To study the effects of JAG-1 on silencing TRAIP(tumor necrosis factor receptor associated factor interaction protein)after regulating Notch signaling pathway on the proliferation and migration of gastric adenocarcinoma cells.[Methods]Gastric adenocarcinoma cells were categorized into si-NC+DMSO(control+DMSO),si-TRAIP#1+DMSO(transfected with TRAIP+DMSO),si-NC+JAG-1(control+JAG-1),and si-TRAIP#1+JAG-1(transfected with TRAIP+JAG-1),and the proliferation of the cells was detected by CCK-8 assay and plate colony formation assay.Transwell assay was used to detect cell migration,and Western blot was adopted to detect the expression of proliferation-associated protein CyclinD1,migration-associated protein MMP2,and key proteins of Notch signaling pathway Notch1,Hes1 and Jagged1.[Results]Compared with siTRAIP#1+DMSO,the gastric adenocarcinoma cells in si-TRAIP#1+JAG-1 group showed increased proliferation and migration(P<0.05),and there was a significant increase in the expression of CyclinD1,MMP2,Notch1,Hes1,and Jagged1(P<0.05).[Conclusions]After TRAIP knockdown,JAG-1 increased not only the proliferation and migration ability of gastric adenocarcinoma cells,but also the expression of key proteins of Notch signaling pathway Notch1,Hes1,and Jagged1.

Inhibitory effects of dobutamine on human gastric adenocarcinoma

AIM: To explore the inhibitory effects of dobutamine on gastric adenocarcinoma cells.

Study on the Correlation between the Expression of Angiogenic Factor VEGF and Microsatellite Instability in Gastric Adenocarcinoma

Objective: To investigate the correlation between the microsatellite instability (MSI) and the expression of vascular endothelial growth factor (VEGF) in gastric adenocarcinoma. Methods: PCR SSCP method was used to detect MSI of thirty cases with gastric adenocarcinoma at five loci in each patient. Expression of VEGF was examined by the method of immunohistochemistry. Results: The positive of MSI was in 13 patients out of 30 patients (43.4%) in our study. Positive VEGF Immunostaining was detected in 18 patients (60.0%). VEGF was decreased in microsatellite instability high (MSI H) gastric adenocarcinoma. Conclusion: MSI H and microsatellite stable (MSS) gastric adenocarcinoma may follow a different pathway of angiogenesis. The low frequency of VEGF expression among MSI H cancer may partially explain why these cancers are less aggressive.

Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil

AIM：To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics.METHODS： Methylation-specific PCR （MSP） assay was performed in 13 nonneoplastic gastric adenocarcinorna, 30 intestinal-type gastric adenocarcinorna and 35 diffuse-type gastric adenocarcinorna samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher＇s exact test to assess associations between rnethylation status and clinico-pathological characteristics.RESULTS： Hypermethylation frequencies of CDH1, FHIT, MTAPand PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hyperrnethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hyperrnethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender.CONCLUSION： Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.

-765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

Effects of tachyplesin and n-sodium butyrate on proliferation and gene expression of human gastric adenocarcinoma cell line BGC-823

AIM： To investigate the effects of tachyplesin and n-sodium butyrate on proliferation and gene expression of human gastric adenocarcinoma cell line BGC-823. METHODS： Effects of tachyplesin and n-sodium butyrate on proliferation of BGC-823 cells were determined with trypan blue dye exclusion test and HE staining. Effects of tachyplesin and n-sodium butyrate on cell cycle were detected by flow cytometry. Protein levels of c-erbB-2, c-myc, p53 and p16 were examined by immunocytochemistry. RESULTS： The inhibiting effects were similar after 2.0 mg/L tachyplesin and 2.0 mmol/L n-sodium butyrate treatment, the inhibitory rate of cellular growth was 62.66% and 60.19% respectively, and the respective maximum mitotic index was decreased by 49.35% and 51.69% respectively. Tachyplesin and n-sodium buD/rate treatment could markedly increase the proportion of cells at G0/G1 phase and decrease the proportion at S phase. The expression levels of oncogene c-erbB-2, c-myc, and mtp53 proteins were down-regulated while the expression level of tumor suppressor gene p16 protein was up-regulated after the treatment with tachyplesin or n-sodium buD/rate. The effects of 1.0 mg/L tachyplesin in combination with 1.0 mmol/L n-sodium butyrate were obviously superior to their individual treatment in changing cell cycle distribution and expression of c-erbB-2, c-myc, mtp53 and p16 protein. The inhibitory rate of cellular growth of BGC-823 cells after combination treatment was 62.29% and the maximum mitotic index wasdecreased by 51.95%. CONCLUSION： Tachyplesin as a differentiation inducer of tumor cells has similar effects as n-sodium butyrate on proliferation of tumor cells, expression of correlative oncogene and tumor suppressor gene. It also has a synergistic effect on differentiation of tumor cells.

Relationship between expression and distribution of cyclooxygenase-2 and bcl-2 in human gastric adenocarcinoma

AIM: To explore expression and distribution features of COX-2 and bcl-2 in human gastric adenocarcinoma tissues and to study its biological significance.METHODS: Totally 36 human gastric carcinoma samples were enrolled in this study (cardiac adenocarcinoma 16 cases, distal gastric adenocarcinoma 20 cases). The expressions of COX-2 and bcl-2 in cancerous tissues and corresponding para-cancerous tissues were investigated by immunohistochemistry using COX-2 polyclonal antibody and bcl-2 monoclonal antibody. The normal gastric mucosa tissues were used as control.RESULTS: The expressions of COX-2 and bcl-2 in gastric carcinoma were significantly higher than that in the paracancerous tissues (77.8% vs 47.2%, P＜0.01, 80.56% vs 58.33%, P＜0.05). The expression of COX-2 in cardiac adenocarcinoma was remarkably higher than that in the distal gastric carcinoma (93.8% vs 65.0%, P＜0.01). The expression of COX-2 was mainly localized in the cytoplasm of tumor cells and partly in the nucleus. There is a transition of the COX-2 cytoplasmic positivity to nucleic in tumor cells with the increase of gastric carcinoma pathological grade. Interstitial macrophages, fibroblasts and vascular endothelial cells also expressed COX-2. The tissues with higher expression of COX-2 also expressed high level of bcl-2 protein.CONCLUSION: Abnormal expression pattern of COX-2within the tissues of human gastric cancer is correlated with tumor location and lymph node metastasis. COX-2may regulate expression of apoptosis suppressor gene (bcl-2) through interaction of tumor cells and stromal cells and play an important role in the generation and development of tumors, which will be of great help in developing new methods for antitumor therapy.

Polymorphism of -765G > C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection:A study from northern India

AIM: To investigate -765G > C COX-2 polymorphism and H pylori infection in patients with gastric adenocarcinoma, peptic ulcer disease (PUD) and non- ulcer dyspepsia (NUD). METHODS: We enrolled 348 adult patients (62 gastric adenocarcinoma, 45 PUD and 241 NUD) undergoing upper gastrointestinal endoscopy at two referral centers between September, 2002 and May, 2007. H pylori infection was diagnosed when any of the four tests (RUT, culture, histopathology and PCR) were positive. Genotyping for -765G > C polymorphism of COX-2 was performed by PCR-RFLP analysis. RESULTS: Frequency of C carrier had significantassociation with gastric adenocarcinoma as compared to NUD [77.4% vs 29%, P < 0.001, odds ratio (OR) 8.20; 95% confidence interval (95% CI), 4.08-16.47] and PUD (77.4% vs 31.1%, P < 0.001; OR 8.04; 95% CI, 3.25-19.90). Risk of gastric adenocarcinoma was significantly higher in patients having C carrier with (OR 7.83; 95% CI 3.09-19.85) and without H pylori infection (OR 7.06; 95% CI, 2.61-19.09). Patients with C carrier and H pylori infection had significant risk for the development of PUD (P < 0.001; OR 5.65; 95% CI, 2.07-15.34). CONCLUSION: -765G > C COX-2 polymorphism with or without H pylori could be a marker for genetic susceptibility to gastric adenocarcinoma. COX-2 polymorphism in presence of H pylori infection might be useful in predicting the risk of PUD.

MYC and gastric adenocarcinoma carcinogenesis

MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacterpylori （Hpylon] and clinical applications.

Inducible nitric oxide synthase, nitrotyrosine and apoptosis in gastric adenocarcinomas and their correlation with a poor survival

AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma.METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression wasdetected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOSexpression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P＜0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high Ais (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low Ais (0.79%; 47.14%) (P= 0.001). COX's multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69).CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival.

Elevated risk for gastric adenocarcinoma can be predicted from histomorphology

The number of patients with gastric cancer has more than doubled since 1985 in developing countries. Thus, the questions of whether it can be predicted from gastritis morphology, who is at risk and who has a lower risk of developing gastric carcinoma are raised. H pylori-infection leads to erosions, ulcerations, carcinoma, mucosa associated lymphoid tissue (MALT)- lymphoma and extragastric diseases only in some individuals. The frequency of ulcerations among H pylori-infected individuals is estimated to be 13%, gastric cancer about 1% and MALT lymphoma around 0.1%. In the literature a multistep model from chronic active H pylori -infection through multifocal atrophy, intestinal metaplasia, dysplasia (intraepithelial neoplasia) and carcinoma has been described. But this model cannot be applied to all routine cases. Since risk factors such as metaplasia and atrophy are paracancerous rather than precancerous conditions, this raises the question whether there is a better morphological marker. Differences in topography, grade and activity of Helicobacter gastritis in the antrum and corpus might be good markers for identifying those who are at risk of developing gastric cancer. It is known that the so-called corpus dominant H pylori gastritis is found more frequently among individuals with early and advanced gastric cancer and within high risk populations. This is valid both for first- degree relatives of gastric cancer patients and for patients with gastric adenoma and hyperplastic polyps. In conclusion, corpus-dominant H pylori gastritis is significantly more common in patients with advanced and early gastric cancer, first-degree relatives of patients with gastric cancer, patients with gastric adenoma and gastric hyperplastic polyps. Therefore, all these patients are at risk of developing gastric cancer. Next, the question of who is at risk of developing corpus-dominant gastritis is raised. It appears that patients with a low acid output more frequently develop gastric cancer. Eradication therapy is never performed too early but probably sometimes too late after the patients pass a “point of no return”. Large prospective long term studiesare necessary to prove this and identify new reliable markers for gastric cancer development.

Twist 1 correlates with poor differentiation and progression in gastric adenocarcinoma via elevation of FGFR2 expression

AIM: To explore the correlation between Twist-related protein (Twist)1, fibroblast growth factor receptor (FGFR)2 and gastric adenocarcinoma differentiation and progression.

MiR-96-5p inhibition induces cell apoptosis in gastric adenocarcinoma

BACKGROUND Gastric adenocarcinoma(GAC)mortality rates have remained relatively changed over the past 30 years,and it continues to be one of the leading causes of cancerrelated death.AIM To search for novel miRNAs related to GAC prognosis and further investigate the effect of miR-96-5p on MGC-803 cells.METHODS The miRNA expression profile data of GAC based on The Cancer Genome Atlas were obtained and used to screen differently expressed miRNAs(DEMs)and DEMs related to GAC prognosis.Then,the expression of DEMs related to GAC prognosis was identified in GAC tumor samples and adjacent normal samples by qRT-PCR.The target gene,ZDHHC5,of miR-96-5p was predicted using TargetScan,miRTarBase,and miRDB databases and confirmed by luciferase reporter assay.Furthermore,MGC-803 cells were transfected with inhibitor NC,miR-96-5p inhibitor,si-ZDHHC5,or miR-96-5p inhibitor+si-ZDHHC5,and then cell apoptosis was detected by flow cytometry.The expression of ZDHHC5,Bcl-2,and COX-2 was detected using western blotting.RESULTS A total of 299 DEMs and 35 DEMs related to GAC prognosis were screened based on The Cancer Genome Atlas.Then compared with adjacent normal samples,the levels of miR-96-5p,miR-222-5p,and miR-652-5p were remarkably increased,while miR-125-5p,miR-145-3p,and miR-379-3p levels were reduced in GAC tumor samples(P<0.01),which were consistent with bioinformatics analysis.Furthermore,ZDHHC5 was defined as a direct target gene of miR-96-5p.miR-96-5p inhibition increased the number of apoptotic cells as well as promoted the expression of ZDHHC5,Bcl-2,and COX-2 in MGC-803 cells(P<0.01).After ZDHHC5 inhibition,the number of apoptotic cells and the expression of ZDHHC5,Bcl-2,and COX-2 were reduced.The addition of an miR-96-5p inhibitor partly reversed these effects(P<0.01).CONCLUSION Our findings identified six miRNAs related to GAC prognosis and suggested that downregulated miR-96-5p might induce cell apoptosis via upregulating ZDHHC5 expression in MGC-803 cells.

Possible involvement of leptin and leptin receptor in developing gastric adenocarcinoma

AIM： To investigate the expression of leptin and leptin receptor （ob-R） in intestinal-type gastric cancer and precancerous lesions, and to explore the possible mechanism and role of the leptin system in developing intestinal-type gastric adenocarcinoma.METHODS： Immunohistochemistry was performed to examine the expression of leptin and leptin receptor in archival samples of gastric adenocarcinoma and preneoplastic lesions, including intestinal metaplasia and mild to severe gastric epithelial dysplasia. Positive staining was identified and percentage of positive staining was graded.RESULTS： Dual expression of leptin and leptin receptor were detected in 80% （16/20） intestinal metaplasia, 86.3% （25/30） mild gastric epithelial dysplasia, 86.7% （26/30） moderate gastric epithelial dysplasia, 93.3% （28/30） severe gastric epithelial dysplasia, 91.3% （55/60） intestinal-type gastric adenocarcinoma and 30.0% （9/30） diffuse-type gastric carcinoma. The percentage of dual expression of leptin and leptin receptor in intestinal-type gastric adenocarcinoma was significantly higher than that in diffuse-type gastric adenocarcinoma （χ^2 = 37.022, P〈0.01）.CONCLUSION： Our results indicate the presence of an autocrine loop of leptin system in the development of intestinal-type gastric adenocarcinoma.