Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.

Identification of functional genes regulating gastric cancer progression using integrated bioinformatics analysis

BACKGROUND Gastric cancer(GC)is one of the most common cancers and has a poor prognosis.Treatment of GC has remained unchanged over the past few years.AIM To investigate the potential therapeutic targets and related regulatory biomarkers of GC.METHODS We obtained the public GC transcriptome sequencing dataset from the Gene Expression Omnibus database.The datasets contained 348 GC tissues and 141 healthy tissues.In total,251 differentially expressed genes(DEGs)were identified,including 187 down-regulated genes and 64 up-regulated genes.The DEGs’enriched functions and pathways include Progesterone-mediated oocyte maturation,cell cycle,and oocyte meiosis,Hepatitis B,and the Hippo signaling pathway.Survival analysis showed that BUB1,MAD2L1,CCNA2,CCNB1,and BIRC5 may be associated with regulation of the cell cycle phase mitotic spindle checkpoint pathway.We selected 26 regulated genes with the aid of the protein-protein interaction network analyzed by Molecular Complex Detection.RESULTS We focused on three critical genes,which were highly expressed in GC,but negatively related to patient survival.Furthermore,we found that knockdown of Yu K et al.Biochemical analysis in GC WJCC https://www.wjgnet.com 5024 July 26,2023 Volume 11 Issue 21 BIRC5,TRIP13 or UBE2C significantly inhibited cell proliferation and induced cell apoptosis.In addition,knockdown of BIRC5,TRIP13 or UBE2C increased cellular sensitivity to cisplatin.CONCLUSION Our study identified significantly upregulated genes in GC with a poor prognosis using integrated bioinformatics methods.

Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation

AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital.GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTS Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), immunohistochemically.CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer.

Increased expression of cyclooxygenase-2 in first-degree relatives of gastric cancer patients

AIM: To study the expression of cyclooxygenase-2 (COX-2)in human gastric cancer tissues and their paired adjacent mucosa, as well as mucosa from gastric antrum and corpus of the first-degree relatives of the recruited cancer patients.METHODS: The expression of COX-2 mRNA in 38 patients with gastric cancer and their 29 first-degree relatives and 18 healthy controls was assessed by the real time RT-PCR.The expression of COX-2 protein was determined by Western blot.RESULTS: A marked increase in COX-2 mRNA expression was found in 20 of 37 (54%) cancerous tissues compared to their respective paired normal mucosa (P＜0.001).Interestingly, increased COX-2 mRNA expression was also found in mucosa of the corpus (6/29) and antrum (13/29)of their first-degree relatives. Increased COX-2 mRNA expression was more frequently observed in the antrum biopsies from cancer patients than in the antrum biopsies from healthy controls (P＜0.05). In addition, 3 of 23 (13%)patients with atrophic mucosa and 6 of 35 (17%) patients with intestinal metaplasia showed increased COX-2 mRNA expression. Furthermore, COX-2 expression increased in H pylori-positive tissues, especially in antrum mucosa.CONCLUSION: Increased COX-2 expression is involved in gastric carcinogenesis, and may be necessary for maintenance of the malignant phenotype and contribute to Helicobacterpylori-associated malignant transformation.

Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation:A case report and review of literature

BACKGROUND Both hepatoid adenocarcinoma of the stomach(HAS)and neuroendocrine differentiation(NED)are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes.HAS with NED is even rarer.CASE SUMMARY Here,we report a 61-year-old man with HAS with NED,as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule.Distal gastrectomy was performed,and pathological examination led to the diagnosis of HAS with NED.However,liver metastases occurred 6 mo later despite adjuvant chemotherapy,and the patient died 27 mo postoperatively.CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases.We first report the detailed processes of the treatment and development of HAS with NED,providing an important reference for the clinical diagnosis and treatment of this condition.

Three-microRNA signature identified by bioinformatics analysis predicts prognosis of gastric cancer patients

AIM To identify multiple micro RNAs(mi RNAs) for predicting the prognosis of gastric cancer(GC) patients by bioinformatics analysis.METHODS The original microarray dataset GSE93415,which included 20 GC and 20 tumor adjacent normal gastric mucosal tissues,was downloaded from the Gene Expression Omnibus database and used for screening differentially expressed mi RNAs(DEMs).The cutoff criteria were P < 0.05 and fold change > 2.0.In addition,we acquired the mi RNA expression profiles and clinical information of 361 GC patients from The Cancer Genome Atlas database to assess the prognostic role of the DEMs.The target genes of mi RNAs were predicted using Target Scan,mi RDB,mi RWalk,and DIANA,and then the common target genes were selected for functional enrichment analysis.RESULTS A total of 110 DEMs including 19 up-regulated and 91 down-regulated mi RNAs were identified between 20 pairs of GC and tumor adjacent normal tissues,and the Kaplan-Meier survival analysis found that a threemi RNA signature(mi R-145-3 p,mi R-125 b-5 p,and mi R-99 a-5 p) had an obvious correlation with the survival of GC patients.Furthermore,univariate and multivariate Cox regression analyses indicated that the three-mi RNA signature could be a significant prognostic marker in GC patients.The common target genes of the three mi RNAs are added up to 108 and used for Gene Functional Enrichment analysis.Biological Process and Molecular Function analyses showed that the target genes are involved in cell recognition,gene silencing and nucleic acid binding,transcription factor activity,and transmembrane receptor activity.Cellular Component analysis revealed that the genes are portion of nucleus,chromatin silencing complex,and TORC1/2 complex.Biological Pathway analysis indicated that the genes participate in several cancer-related pathways,such as the focal adhesion,PI3 K,and m TOR signaling pathways.CONCLUSION This study justified that a three-mi RNA signature could play a role in predicting the survival of GC patients.

Feasibility study on expanded indication for endoscopic submucosal dissection of intramucosal poorly differentiated early gastric cancer

AIM: To identify clinicopathological factors predictive of lymph node metastasis(LNM) in intramucosal poorly differentiated early gastric cancer(EGC), and further to expand the possibility of using endoscopic submucosal dissection(ESD) for the treatment of intramucosal poorly differentiated EGC.METHODS: Data for 81 surgically treated patients with intramucosal poorly differentiated EGC were collected, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios(ORs) with 95% confidence intervals(CIs) were calculated. Several clinicopathologic factors were investigated to identify predictive factors for lymph nodes metastasis, including gender, age, family history of gastric cancer, number of tumors, tumor location, ulceration, tumor size, macroscopic type, lymphatic vessel involvement, and signet-ring-cell component.RESULTS: Tumor size(OR = 7.273, 95%CI: 1.246-29.918, P = 0.042), lymphatic vessel involvement(OR = 42.219, 95%CI: 1.923-97.052, P = 0.018) and signet-ring-cell component(OR = 17.513, 95%CI: 1.647-77.469, P = 0.034) that were significantly associated with LNM by univariate analysis, were found to be significant and independent risk factors for LNM by multivariate analysis. However, gender, age, family history of gastric cancer, number, location, ulceration and macroscopic type of tumor were found not to be associated with LNM. Of these 81 patients diagnosed with intramucosal poorly differentiated EGC, 7(8.6%) had LNM. The LNM rates were 9.1%, 22.2% and 57.1%, respectively, in cases with one, two and three of the risk factors. There was no LNM in 54 patients without the three risk clinicopathological factors.CONCLUSION: Tumor size, lymphatic vessel involvement and signet-ring-cell component are independently associated with the presence of LNM in intramucosal poorly differentiated EGC. Thus, these three risk factors may be used as a simple criterion to expand the possibility of using ESD for the treatment of intramucosal poorly differentiated EGC.

Mucin phenotype of gastric cancer and clinicopathology of gastric-type differentiated adenocarcinoma

Differentiated adenocarcinoma of the stomach is classified into gastric or intestinal phenotypes based on mucus expression. Recent advances in mucin histochemistry and immunohistochemistry have highlighted the importance of such a distinction, and it is important clinically to distinguish between gastricand intestinal-type differentiated adenocarcinoma. However, a clinical and pathological diagnosis of this type is often difficult in early gastric cancer because of histological similarities between a hyperplastic epithelium and lowgrade atypia. Furthermore, determining tumor margins is often difficult, even with extensive preoperative examination. It is therefore critical to consider these diagnostic difficulties and different biological behaviors with high malignant potential when treating patients with gastric-type differentiated adenocarcinoma.

Expression and clinical significance of serum lipoprotein(a) in patients with gastric cancer

Objective This study aimed to investigate the expression and clinical significance of serum lipoprotein(a) [LP(a)] in patients with gastric cancer. Methods Two hundred and twenty-two patients with gastric cancer(gastric cancer group) were selected from 2015 to 2017 [mean age(58.40 ± 10.40) years], as were 101 healthy persons [normal age group, mean age(58.18 ± 11.42) years]. Fasting blood samples were collected and evaluated by immunoturbidimetry with a biochemical analyzer. LP(a) concentration was observed and its difference was compared. Results There was no significant correlation between LP(a) and tumor stage(P > 0.05). Compared with the control group, the level of LP(a) in the male gastric cancer group was significantly higher than that in the control group(P < 0.05). In the subgroup analysis, the level of LP(a) and abnormal rate showed an increasing trend among patients with stages I–IV gastric cancer. The level of LP(a) in poorly differentiated gastric cancer patients was higher than that in the high middle differentiation group(P < 0.05). There was no significant difference in LP(a) levels among patients with different pathological types of gastric cancer(P > 0.05). Conclusion LP(a) was correlated with the occurrence, development and differentiation of gastric cancer, but not with the pathological classification of gastric cancer. Serum LP(a) concentration may be used as an indicator for the staging and prognosis of gastric cancer, but the specific underlying mechanism remains to be further studied.

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.METHODS:We evaluated Twist1 and FGFR2 in 52 gastric adenocarcinoma samples by immunohistochemistry and quantitative real time polymerase chain reaction,and analyzed the correlation between Twist1,FGFR2 and cancer differentiation.We also detected Twist1 and FGFR2 expression in gastric adenocarcinoma cell lines,and evaluated Twist1 influence on FGFR2 expression.In addition,we studied the role of FGFR2 in Twist1-promoted cancer progression,including proliferation,invasion and epithelial-mesenchymal transition(EMT).RESULTS:Twist1 and FGFR2 were detected in almost all the gastric adenocarcinoma samples.Twist1(P=0.0213)and FGFR2(P=0.0310)m RNA levels had a significant association with gastric adenocarcinoma differentiation.Moreover,Twist1 and FGFR2 expression in poorly differentiated cells(SNU-1 and SNU-16)was notably higher than in well-differentiated cells(MKN-7 and MKN-28).In poorly differentiated gastric adenocarcinomas,FGFR2 m RNA level was significantly positively correlated with Twist1 m RNA level(P=0.004).Twist1 was proved to promote FGFR2 by regulating Twist1 expression by knockdown and overexpression.Additionally,Twist1 could induce proliferation,invasion and EMT in gastric cancer;of these,FGFR2 was required for invasion and EMT,rather than proliferation.CONCLUSION:Twist1 and FGFR2 are highly associated with differentiation of gastric adenocarcinoma;Twist1 can facilitate invasion and EMT in gastric adenocarcinoma via promotion of FGFR2 expression.

Bioinformatics Analysis and Identification of Potential Genes Associated with Pathogenesis and Prognosis of Gastric Cancer

Objective Gastric cancer(GC)is a deadly cancer and a challenging public health problem globally.This study aimed to analyze potential genes associated with pathogenesis and prognosis of gastric cancer.Methods This work selected the overlapping differentially expressed genes(DEGs)in GC from four datasets,the GSE29272,GSE29998,GSE54129 and GSE118916 Gene Expression Omnibus databases.These DEGs were used to carry out comprehensive bioinformatic analysis to analyze the related functions and pathways enriched,the relative expression levels and immune infiltrates,the prognostic characteristics and the interaction network.Results In total,55 DEGs increased while 98 decreased in their expression levels.For those DEGs with increased expression,they were mostly concentrated on“focal adhesion”and“ECM-receptor interaction”,whereas DEGs with decreased expression were mostly associated with“gastric acid secretion”and“drug metabolism cytochrome P450”.MCODE and ClueGO results were then integrated to screen 10 hub genes,which were FN1,COL1A1,COL3A1,BGN,TIMP1,COL1A2,LUM,VCAN,COL5A2 and SPP1.Survival analysis revealed that higher expression of the ten hub genes significantly predicted lower overall survival of GC patients.TIMP1 was most significantly related to neutrophils,CD8+T cells,as well as dendritic cells,while LUM was most significantly related to macrophages.Conclusion Immunohistochemistry results and functional testing showed that the expression of COL5A2 was elevated in GC and that it might be a key gene in GC tumorigenesis.

Silence of HIN-1 expression through methylation of its gene promoter in gastric cancer

AIM: To clarify the role of high in normal-1 (HIN-1) gene promoter methylation during gastric cancer development. METHODS: Gastric cancer cell lines and tissue specimens were analyzed for expression of HIN-1 mRNA and protein using the semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The methylation of the HIN-1 gene promoter was detected in gastric carcinoma cells and tissues using methylation-specific polymerase chain reaction. The 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay and flow cytometry were used to assess the changes in behaviors of gastric cancer cells with or without 5-aza-2’-deoxycytidine treatment. RESULTS: HIN-1 was not expressed in 4 of 5 gastric cancer cell lines. The demethylation reagent 5-aza-2’-deoxycytidine was able to induce or upregulate HIN-1 expression in gastric cancer cell lines, which is associated with reduction of tumor cell viability. Furthermore, methylation of the HIN-1 gene promoter was shown in 57.8% (26/45) of the primary gastric cancer and 42.1% (17/38) of adjacent tissue samples, but was not shown in normal gastric mucosa (0/10). From the clinicopathological data of the patients, methylation of the HIN-1 gene promoter was found to be associated with tumor differentiation (P = 0.000). CONCLUSION: High methylation of HIN-1 gene promoter results in silence of HIN-1 expression in gastric cancer. 5-aza-2’-deoxycytidine reverses HIN-1 methylation and reduces viability of gastric cancer cells.

Use of lectin microarray to differentiate gastric cancer from gastric ulcer

AIM:To investigate the feasibility of lectin microarray for differentiating gastric cancer from gastric ulcer.METHODS:Twenty cases of human gastric cancer tissue and 20 cases of human gastric ulcer tissue were collected and processed.Protein was extracted from the frozen tissues and stored.The lectins were dissolved in buffer,and the sugar-binding specificities of lectins and the layout of the lectin microarray were summarized.The median of the effective data points for each lectin was globally normalized to the sum of medians of all effective data points for each lectin in one block.Formalin-fixed paraffin-embedded gastric cancer tissues and their corresponding gastric ulcer tissues were subjected to Ag retrieval.Biotinylated lectin was used as the primary antibody and HRP-streptavidin as the secondary antibody.The glycopatterns of glycoprotein in gastric cancer and gastric ulcer specimens were determined by lectin microarray,and then validated by lectin histochemistry.Data are presented as mean±SD for the indicated number of independent experiments.RESULTS:The glycosylation level of gastric cancer was significantly higher than that in ulcer.In gastric cancer,most of the lectin binders showed positive signals and the intensity of the signals was stronger,whereas the opposite was the case for ulcers.Significant differences in the pathological score of the two lectins were apparent between ulcer and gastric cancer tissues using the same lectin.For MPL and VVA,all types of gastric cancer detected showed stronger staining and a higher positive rate in comparison with ulcer,especially in the case of signet ring cell carcinoma and intra-mucosal carcinoma.GalNAc bound to MPL showed a significant increase.A statistically significant association between MPL and gastric cancer was observed.As with MPL,there were significant differences in VVA staining between gastric cancer and ulcer.CONCLUSION:Lectin microarray can differentiate the different glycopatterns in gastric cancer and gastric ulcer,and the lectins MPL and VVA can be used as biomarkers.

Bioinformatics analysis of potential hub genes associated with biological characteristics and survival in patients with gastric cancer

Objective Gastric cancer(GC)is a serious threat to human health.In this study,we aimed to explore the differentially expressed genes(DEGs)and identify potential targets for the treatment of GC.Methods The gene expression profile of GSE79973 which compared tissue samples from gastric cancer patients and healthy individuals,downloaded from the GEO database,was submitted to the GCBI online analysis platform to screen for DEGs.Gene ontology(GO)analysis,pathway analysis,and construction of networks,including gene signal and gene co-expression networks,were performed to identify the core DEGs.Survival analysis was performed to determine the relationship between these genes and patient survival time.Results Nine hundred eighty-three genes were identified as DEGs(P<0.001;FC>2).GO analysis showed that DEGs were primarily involved in processes such as angiogenesis,cell metabolism,cell adhesion,redox processes,and cell migration.The metabolism of xenobiotics by cytochrome P450,ECM-receptor interaction,drug metabolism by cytochrome P450,metabolic pathways,and the PI3K-Akt signaling pathway were significantly enriched in pathway analysis.Genes such as UGT2B15,Hepatocyte growth factor(HGF),Nidogen-2(NID2),Follistatin-like protein 1(FSTL1),and Inhibin beta A chain(INHBA)were closely linked to other genes in the network.Survival analyses indicated that HGF,NID2,FSTL1,and INHBA expression levels were inversely correlated with survival time in patients with gastric cancer.Conclusion HGF,NID2,FSTL1,and INHBA may be potential key genes associated with the biological characteristics and survival in patients with gastric cancer.

Identification of key pathways and genes from gastric precancerous lesions to gastric cancer by integrated bioinformatics analysis

Objective:This work aimed to illuminate the potential key genes and pathways in GC tumorigenesis based on bioinfOrmatics analysis.Methods:The differentially expressed genes(DEGs)between GPL tissue samples and GC tissue samples were investigated using the GSE55696 and GSE87666 microarray data from the Gene Expression Omnibus(GEO)database.DEGs were identified by an empirical Bayes method based on the Limma R package.Then,KEGG and GO enrichment analyses of DEGs were performed followed by protein-protein interaction(PPI)network construction.Finally,the overall survival(OS)analysis of key genes was performed by the Kaplan-Meier plotter online tool.Results:A total of 250 DEGs were obtained,of which 216 were up-regulated and 34 were down-regulated.KEGG pathways analysis showed that the up-regulated DEGs were enriched in cytokine-cytokine receptor interaction,chemokine signaling pathway,metabolic pathways,PI3K-Akt signaling pathway,NF-kappa B signaling pathway,and other signaling pathways about cancer,while no down-regulated pathways were enriched.A PPI network of DEGs was constructed with 117 nodes and 660 edges,and 20 genes were selected as hub genes owing to high degrees in the network.According to the Kaplan-Meier analysis,6 out of 20 hub genes including CCR7,FPR1,C3,CXCR5,GNB4,and PPBP with high mRNA expression were associated with poor OS for GC patients.Conclusion:The results of this study provide possible factors for the occurrence of GC,and the identification of the genes and pathways associated with the progression from GPL to GC provides valuable data for investigating the pathogenesis in future studies.

Tumor budding in gastric cancer

The tumor,nodes,metastasis(TNM)staging system has long been the gold standard for the classification and prognosis of solid tumors.However,the TNM staging system is not without limitations.Prognostic heterogeneity exists within patients at the same stage.Therefore,the pursuit of other biomarkers with the potential to classify patients with cancer has never stopped.One of them,tumor budding(TB),has gained much success in colorectal cancer.In recent years,TB in gastric cancer has attracted much attention from researchers,beginning to reveal the molecular and biological aspects of this phenomenon in gastric cancer,and has emerged as a promising prognostic biomarker in gastric cancer,predicting disease progression and unfavorable survival.Therefore,it is time and essential to provide a holistic overview of TB in gastric cancer,which has not been achieved and is the aim of this review.

Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin & eosin (HE) staining was used for histological evaluation, including the type (Lauren's classifi cation) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P = 0.002). A signifi cant relation was seen between the grade of tumor and the expression of CD44 (P = 0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P = 0.008); and this was more prominent in the intestinal (P = 0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients.

Does the discrepancy in histologic differentiation between a forceps biopsy and an endoscopic specimen necessitate additional surgery in early gastric cancer?

AIM To investigate the clinicopathological variables in early gastric cancer(EGC) patients in relation to differentiation discrepancy.METHODS The data of 265 specimens from 240 patients with EGC, who had undergone radical operation at Hallym University Sacred Heart Hospital from 2010 to 2015, were retrospectively analyzed. We evaluated clinical, endoscopic, and histopathological data according to histological discrepancy.RESULTS Clinically significant discrepancy rate showed the difference in differentiated type(well and moderately differentiated) and undifferentiated type(poorly differentiated and signet ring cell) between endoscopic biopsies and postoperative specimens was 9.4%(25/265). There were no differences in tumor location, size, gross pattern, and number of biopsies. Specimens having histological discrepancy showed more submucosal invasion(72.0% vs 49.6%, P = 0.033) and lymph node involvement(24.0% vs 7.9%, P = 0.009) than specimens having non-discrepancy. The rate of a positive epidermal growth factor receptor status was higher in specimens having discrepancy than in specimens having non-discrepancy(81.0% vs 55.4%, P = 0.035).CONCLUSION The discordance of histologic differentiation is associated with higher submucosal invasion and lymph node metastases in EGC. Patients have histological discrepancy may require additional surgical treatments.

Tumor differentiation as related to sentinel lymph node status in gastric cancer

AIM:To investigate the influence of tumor grade on sentinel lymph node(SLN)status in patients with gastric cancer(GC).METHODS:We retrospectively studied 71 patients with GC who underwent SLN mapping during gastric surgery to evaluate the relationship between SLN status and tumor grade.RESULTS:Poorly differentiated tumors were detected in 50/71 patients,while the other 21 patients had moderately differentiated tumors.SLNs were identified in 58/71 patients(82%).In 41 of the 58 patients that were found to have stained nodes(70.7%),the tumor was of the poorly differentiated type(groupⅠ),while in the remaining patients with stained nodes 17/58(29.3%),the tumor was of the moderately differentiated type(groupⅡ).Positive SLNs were found in22/41 patients in group I(53.7%)and in 7/17 patients in groupⅡ(41.2%)(P=0.325).The rate of positivity for the SLNs in the two groups(53.7%vs 41.2%)was not statistically significant(P=0.514).CONCLUSION:Most of our patients were found to have poorly differentiated adenocarcinoma of the stomach and there was no correlation between tumor grade and SLN involvement.

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection

BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely related to the safety and efficacy of ESD.