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.

DNA and histone methylation in gastric carcinogenesis

Epigenetic alterations contribute significantly to the development and progression of gastric cancer,one of the leading causes of cancer death worldwide.Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA,and these changes lead to transcriptional activation or silencing of the gene.Over the years,the study of epigenetic processes has increased,and novel therapeutic approaches that target DNA methylation and histone modifications have emerged.A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment.Here,we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome.

Helicobacter pylori and oral pathology:Relationship with the gastric infection

Helicobacter pylori(H.pylori)has been found in the oral cavity and stomach,and its infection is one of the most frequent worldwide.We reviewed the literature and conducted a Topic Highlight,which identified studies reporting an association between H.pylori-infection in the oral cavity and H.pylori-positive stomach bacterium.This work was designed to determine whether H.pylori is the etiologic agent in periodontal disease,recurrent aphthous stomatitis(RAS),squamous cell carcinoma,burning and halitosis.Record selection focused on the highest quality studies and meta-analyses.We selected 48 articles reporting on the association between saliva and plaque and H.pylori-infection.In order to assess periodontal disease data,we included 12 clinical trials and 1 meta-analysis.We evaluated 13 published articles that addressed the potential association with RAS,and 6 with squamous cell carcinoma.Fourteen publications focused on our questions on burning and halitosis.There is a close relation between H.pylori infection in the oral cavity and the stomach.The mouth is the first extra-gastric reservoir.Regarding the role of H.pylori in the etiology of squamous cell carcinoma,no evidence is still available.

hsa-miR-29c and hsa-miR-135b differential expression aspotential biomarker of gastric carcinogenesis

AIM: To investigate the expression profiles of hsa-mi R-29 c and hsa-mi R-135 b in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. METHODS: The expression levels of hsa-mi R-29 c and hsa-mi R-135 b in normal gastric mucosa, non-atrophic chronic gastritis, intestinal metaplasia and intestinaltype gastric adenocarcinoma were analysed using quantitative real-time PCR. The difference between hsa-mi R-29 c and hsa-mi R-135 b expression profiles in the grouped samples was evaluated by ANOVA and Student's t-test tests. The results were adjusted for multiple testing by using Bonferroni's correction. P values ≤ 0.05 were considered statistically significant. To evaluate hsa-mi R-29 c and hsa-mi R-135 b expressions as potential biomarkers of gastric carcinogenesis, we performed a receiver operating characteristic curve analysis and the derived area under the curve, and a Categorical Principal Components Analysis. In silico identification of the genetic targets of hsa-mi R-29 c and hsa-mi R-135 b was performed using different prediction tools, in order to identify possible genes involved in gastric carcinogenesis.RESULTS: The expression levels of hsa-mi R-29 c were higher in normal gastric mucosal samples, and decreased progressively in non-atrophic chronic gastritis samples, intestinal metaplasia samples and intestinal-type gastric adenocarcinoma samples. The expression of hsa-mi R-29 c in the gastric lesions showed that non-atrophic gastritis have an intermediate profile to gastric normal mucosa and intestinal-type gastric adenocarcinoma, and that intestinal metaplasia samples presented an expression pattern similar to that in intestinal-type gastric adenocarcinoma. This micro RNA(mi RNA) has a good discriminatory accuracy between normal gastric samples and(1) intestinal-type gastric adenocarcinoma; and(2) intestinal metaplasia, and regulates the DMNT3 A oncogene. hsa-mi R-135 b is up-regulated in non-atrophic chronic gastritis and intestinal metaplasia samples and down-regulated in normal gastric mucosa and intestinal-type gastric adenocarcinoma samples. Non-atrophic chronic gastritis and intestinal metaplasia are significantly different from normal gastric mucosa samples. hsa-mi R-135 b expression presented a greater discriminatory accuracy between normal samples and gastric lesions. This mi RNA was associated with Helicobacter pylori presence in non-atrophic chronic gastritis samples and regulates the APC and KLF4 tumour suppressor genes.CONCLUSION: Our results provide evidence of epigenetic alterations in non-atrophic chronic gastritis and intestinal metaplasia and suggest that hsa-mi R-29 c and hsa-mi R-135 b are promising biomarkers of gastric carcinogenesis.

Latest insights into the effects of Helicobacter pylori infection on gastric carcinogenesis

看起来是在 Helicobacter pylori (H pylori ) 和胃的癌症之间的强壮的协会。我们在胃的致癌作用上关于 H pylori 感染的效果考察了最近的证据，分类进传染病学，胃的粘膜变化的动力学， DNA 损坏，毒力因素，主人因素，和胃的恶意的来源。通过在对源于 H pylori 紧张之间的差别的毒力因素的研究取得的可观的进步，例如 cagA 确实，以及进主人因素，例如基因多型性，包括胃的癌症， H 联系 pylori 的疾病的一个多样的系列把自己正在借给说明。当发展研究上的胃的恶意的潜在的来源与兴趣尚待分晓，建议骨头髓的 Houghton 等推进的新奇假设的影响导出干细胞(BMDC ) 。进一步作为胃的癌症的可行预防在对 H pylori 根除，以及进胃的致癌作用的机制的研究进行，是急切地被等候当前的年并且在以外。

Analysis of the HNF4A isoform-regulated transcriptome identifies CCL15 as a downstream target in gastric carcinogenesis

Objective:Hepatocyte nuclear factor 4α(HNF4 A)has been demonstrated to be an oncogene in gastric cancer(GC).However,the roles of different HNF4 A isoforms derived from the 2 different promoters(P1 and P2)and the underlying mechanisms remain obscure.Methods:The expression and prognostic values of P1-and P2-HNF4 A were evaluated in The Cancer Genome Atlas(TCGA)databases and GC tissues.Then,functional assays of P1-and P2-HNF4 A were conducted both in vivo and in vitro.High-throughput RNA-seq was employed to profile downstream pathways in P1-and P2-HNF4 A-overexpressing GC cells.The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays.Results:HNF4 A amplification was a key characteristic of GC in TCGA databases,especially for the intestinal type and early stage.Moreover,P1-HNF4 A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues(P<0.05),but no significant differences were found in P2-HNF4 A expression(P>0.05).High P1-HNF4 A expression indicated poor prognoses in GC patients(P<0.01).Furthermore,P1-HNF4 A overexpression significantly promoted SGC7901 and BGC823 cell proliferation,invasion and migration in vitro(P<0.01).Murine xenograft experiments showed that P1-HNF4 A overexpression promoted tumor growth(P<0.05).Mechanistically,RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4 A-overexpressing GC cells.Finally,chemokine(C-C motif)ligand 15 was identified as a direct target of P1-HNF4 A in GC tissues.Conclusions:P1-HNF4 A was the main oncogene during GC progression.The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.

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 Helicobacter pylori (H pylori) and clinical applications.

Epigenetic alterations in gastric carcinogenesis

Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogeneoverexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a varietyof methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play impor-tant roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpGisland methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesisand its relevance of clinical implications.

CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis

AIM:To characterize the immune responses including local and systemic immunity induced by infection with H pylori,especially with CagA+ H pylori strains and the underlying immunopathogenesis. METHODS:A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA),the presence of T helper (Th) cells and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMCs),expression of plasma cytokines,and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test,urea 14C breath test,immunoblotting test,flow cytometry ,real time RT-PCR and immunohistochemistry. RESULTS:Of the patients,629 (88.47%) were infected with H pylori ; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains,Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis,while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However,there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection. CONCLUSION:Polarization of Th cell immune responses occurs in patients with CagA+ H pyloriinfection,which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.

Priming the seed:Helicobacter pylori alters epithelial cell invasiveness in early gastric carcinogenesis

Helicobacter pylori(H. pylori) infection is a wellestablished risk factor for the development of gastric cancer(GC), one of the most common and deadliest neoplasms worldwide. H. pylori infection induces chronic inflammation in the gastric mucosa that, in the absence of treatment, may progress through a series of steps to GC. GC is only one of several clinical outcomes associated with this bacterial infection, which may be at least partially attributed to the high genetic variability of H. pylori. The biological mechanisms underlying how and under what circumstances H. pylori alters normal physiological processes remain enigmatic. A key aspect of carcinogenesis is the acquisition of traits that equip preneoplastic cells with the ability to invade. Accumulating evidence implicates H. pylori in the manipulation of cellular and molecular programs that are crucial for conferring cells with invasive capabilities. We present here an overview of the main findings about the involvement of H. pylori in the acquisition of cell invasive behavior, specifically focusing on the epithelial-to-mesenchymal transition, changes in cell polarity, and deregulation of molecules that control extracellular matrix remodeling.

Effect of 1, 25-Dihydroxyvitamin D_3 on Gastric Carcinogenesis Induced by N-Methyl-N'-nitro-N-nitrosoguanidine in Rats

The effect of 1, 25-dihydroxyvitamin D3 (1, 25 (OH)2D3) given in the post-initiation stage of gastric carcinogenesis induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was investigated in male Wistar rats. Gastric carcinogenesis in rats was induced by administration of MNNG (150 mg·L-1) in drinking water. Four weeks after MNNG exposure, the rats were switched to the diet containing 1, 25 (OH)2D3 (2. 5 μg·kg-1 and 5. 0 μg·kg-1) and maintained on the diet. Animals were killed at week 16 and week 32 for immunohistochemical and histopathological studies. At week 16, the proliferating cell nuclear antingen (PCNA) labeling index in epithelium from the glandular stomach of rats that received 1, 25 (OH)2D3 (5.0 μg·kg-1) in combination with MNNG (150 mg·L-1) were significantly higher when compared with the rats receiving MNNG alone. Supplementation of 1, 25 (OH)2D3 (5. 0 μg·kg-1) in the rats' diet caused a dramatic increase in carcinoma incidence, and the number of individual cancer foci in the glandular stomach of rats receiving MNNG at week 32. It was concluded that certain dose of 1, 25 (OH)2D3 enhanced gastric carcinogenesis induced by MNNG in rats.

Histological and ultrastructural changes induced by selenium in early experimental gastric carcinogenesis

AIM: To investigate the effect and significance of selenium in early experimental gastric carcinogenesis.METHODS: Weaning male Wistar rats were divided randomly into normal control group, experiment control group, low selenium (2 mg/L) group and high selenium (4 mg/L) group. Wistar rat gastric carcinogenesis was induced by N-methyl-N-nitro-N-nitroso guanidine (MNNG) (20 mg/kg) gavage daily for 10 d. Na2SeO3 was given by piped drinking 1 wk prior to MNNG gavage. The rats were killed at the 43rd wk. The surface characteristics of gastric mucosa were observed with naked eyes. Histopathologic changes of rat gastric mucosa were observed by HE staining and AB-PAS methods. The changes of cellular ultrastructure were observed under transmission electron microscope. Statistical analysis was carried out by SPSS.RESULTS: The incidence rate of gastric mucosa erosion,hemorrhage and intestinal metaplasia was 0, 45.5%,66.7%, and 92.9%, respectively (92.9% vs45.5%, P＜0.05)in the normal control group, experiment control group,low selenium group, and high selenium group. Leiomyoma formed in the process of inducement of rat gastric carcinoma. Dietary Na2SeO3 (2 and 4 mg/L) slightly increased the incidence rate of leiomyoma (0, 23%, 46.6%, and 46.6%). gastric mucosa did not change in the course of rat gastric carcinogenesis. Dietary Na2SeO3 by pipe drinking could expand the intracellular secretory canaliculus of parietal cells and increase the number of endocrine cells and lysosomes.CONCLUSION: Dietary Na2SeO3 by pipe drinking aggravates gastric erosion, hemorrhage and promotes intestinal metaplasia of gastric mucosa. The mechanism may be related with the function of parietal cells.

Cyr61/CTGF/Nov family proteins in gastric carcinogenesis

Gastric cancer(GC)is the second leading cause of cancer-related death.The poor survival rate may reflect the relatively aggressive tumor biology of GC.Recently,the importance of the tumor microenvironment in carcinogenesis has emerged.In the tumor microenvironment,tumor cells and the surrounding stromal cells aberrantly secrete matricellular proteins capable of modulating carcinogenesis and regulating metastasis.The Cyr61/CTGF/Nov(CCN)proteins are a family of matricellular proteins with variable roles in many physiological and pathological processes.The evidence suggests that CCN family proteins contribute to GC carcinogenic processes.Here,we briefly review recent research on the effects of CCN family proteins in GC carcinogenesis and the development of new targeted agents in this field.

Is NEDD4-1 a negative regulator of phosphatase and tensin homolog in gastric carcinogenesis?

The expression of phosphatase and tensin homolog (PTEN ), a tumor suppressor gene, is frequently downregulated in gastric carcinomas due to mutation, loss of heterozygosity, and promoter hypermethylation. However, it is unknown if additional mechanisms may account for the down-regulation of PTEN expression. While neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) is believed to be a potential dual regulator of PTEN, there are conflicting reports regarding their interaction. To gain further insight into the role of NEDD4-1 and its association with PTEN in gastric carcinoma development, we measured the protein expression of NEDD4-1 and PTEN in gastric mucosae with various pathological lesions and found that NEDD4-1 increased from normal gastric mucosa to intestinal metaplasia and decreased from dysplasia to gastric carcinoma. These changes did not correlate with PTEN expression changes during gastric carcinogenesis. Moreover, we found similar results in protein levels in the primary tumors and adjacent non-tumorous tissues. These results differ from a previous report showing that expression of NEDD4-1 is up-regulated in gastric carcinomas, and show a more complex pattern of NEDD4-1 gene expression during gastric carcinogenesis.

Clinical value of oral contrast-enhanced ultrasonography in diagnosis of gastric tumors

BACKGROUND The incidence of gastric cancer remains high,and it is the sixth most common cancer and the fourth leading cause of cancer deaths worldwide.Oral contrastenhanced ultrasonography is a simple,non-invasive,and painless method for the diagnosis of gastric tumors.AIM To explore the diagnostic value of oral contrast-enhanced ultrasonography for the detection of gastric tumors.METHODS The screening results based on oral contrast-enhanced ultrasonography and electronic gastroscopy were compared with those of the postoperative pathological examination.RESULTS Among 42 patients with gastric tumors enrolled in the study,the diagnostic accordance rate was 95.2%for oral contrast-enhanced ultrasonography(n=40)and 90.5%for electronic gastroscopy(n=38)compared with postoperative pathological examination.The Kappa value of consistency test with pathological findings was 0.812 for oral contrast-enhanced ultrasonography and 0.718 for electronic gastroscopy,and there was no significant difference between them(P=0.397).For the TNM staging of gastric tumors,the accuracy rate of oral contrast enhanced ultrasonography was 81.9%for the overall T staging and 50%,77.8%,100%,and 100%for T1,T2,T3,and T4 staging,respectively.The sensitivity and specificity were both 100%for stages T3 and T4.The diagnostic accuracy rate of oral contrast-enhanced ultrasonography was 93.8%,80%,100%,and 100%for stages N0,N1-N3,M0,and M1,respectively.CONCLUSION The accordance rate of qualitative diagnosis by oral contrast-enhanced ultrasonography is comparable to that of gastroscopy,and it could be used as the preferred method for the early screening of gastric tumors.

Could microbiome analysis be a new diagnostic tool in gastric carcinogenesis for high risk, Helicobacter pylori negative patients?

Helicobacter pylori(H.pylori)has long been believed to be the major colonizer of the stomach,but recent advances in genetic sequencing have allowed for further differentiation of the gastric microbiome and revealed the true complexity of the gastric microbiome.One of the few studies specifically evaluated the microbiome in the H.pylori negative patient population.They concluded that various stages of gastric carcinogenesis are associated with distinct bacterial taxa that could service both a predictive and diagnostic purpose.While the study has some limitations,the conclusions they make are intriguing and should prompt a larger prospective study to be done that spans multiple geographic regions.

Prediction of genetic alterations from gastric cancer histopathology images using a fully automated deep learning approach

BACKGROUND Studies correlating specific genetic mutations and treatment response are ongoing to establish an effective treatment strategy for gastric cancer(GC).To facilitate this research,a cost-and time-effective method to analyze the mutational status is necessary.Deep learning(DL)has been successfully applied to analyze hematoxylin and eosin(H and E)-stained tissue slide images.AIM To test the feasibility of DL-based classifiers for the frequently occurring mutations from the H and E-stained GC tissue whole slide images(WSIs).METHODS From the GC dataset of The Cancer Genome Atlas(TCGA-STAD),wildtype/mutation classifiers for CDH1,ERBB2,KRAS,PIK3CA,and TP53 genes were trained on 360×360-pixel patches of tissue images.RESULTS The area under the curve(AUC)for the receiver operating characteristic(ROC)curves ranged from 0.727 to 0.862 for the TCGA frozen WSIs and 0.661 to 0.858 for the TCGA formalin-fixed paraffin-embedded(FFPE)WSIs.The performance of the classifier can be improved by adding new FFPE WSI training dataset from our institute.The classifiers trained for mutation prediction in colorectal cancer completely failed to predict the mutational status in GC,indicating that DL-based mutation classifiers are incompatible between different cancers.CONCLUSION This study concluded that DL could predict genetic mutations in H and E-stained tissue slides when they are trained with appropriate tissue data.

Toll-Like Receptors as Biomarkers of Gastric Carcinogenesis:Implications for Diagnosis,Prognosis and Treatment

Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. Moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.

Comparative Analysis of the Value of Gastroscopic Biopsy and Surgical Pathology in the Diagnosis of Gastric Cancer

Objective:To explore and analyze the diagnostic value of gastroscopic biopsy and surgical pathology in improving the diagnostic accuracy of gastric cancer.Methods:From May 2019 to June 2020,80 patients with gastric cancer treated in Shuyang Xiehe Hospital were selected and divided into two groups,a control group and a study group,with 40 cases in each group,based on the examination method individually selected by the patients.The patients in the control group were investigated via gastroscopy,while those in the study group were investigated by surgical pathology.The diagnostic values of the two methods were compared and analyzed.Results:The diagnostic accuracy of patients in the study group was 100%,which was higher than that of the control group.The tissue type,lesion morphology,and cancer differentiation of the study group were better than those of the control group.There was significant difference between the two methods(P<0.05).Conclusion:Surgical and pathological examination can improve the diagnostic accuracy of gastric cancer,comprehensively analyze the patient’s condition,and provide corresponding theoretical basis for follow-up treatment,so that patients can obtain more active and effective treatment,reduce pain,and improve their quality of life.

Clinicopathologic and molecular features associated with patient age in gastric cancer

AIM: To compare characteristics and prognosis of gastric cancer based on age.METHODS: A retrospective study was conducted on clinical and molecular data from patients(n =1658) with confirmed cases of gastric cancer in Seoul National University Bundang Hospital(Seoul, South Korea) from 2003 to 2010 after exclusion of patients diagnosed with lymphoma, gastrointestinal stromal tumor, and metastatic cancer in the stomach. DNA was isolated from tumor and adjacent normal tissue,and a set of five markers was amplified by polymerase chain reaction to assess microsatellite instability(MSI). MSI was categorized as high, low, or stable if ≥ 2, 1, or 0 markers, respectively, had changed.Immunohistochemistry was performed on tissue sections to detect levels of expression of p53, human epidermal growth factor receptor(HER)-2, and epidermal growth factor receptor. Statistical analysis of clinical and molecular data was performed to assess prognosis based on the stratification of patients by age(≤ 45 and> 45 years).RESULTS: Among the 1658 gastric cancer patients, the number of patients with an age ≤ 45 years was 202(12.2%; 38.9 ± 0.4 years) and the number of patients> 45 years was 1456(87.8%; 64.1 ± 0.3 years).Analyses revealed that females were predominant inthe younger group(P < 0.001). Gastric cancers in the younger patients exhibited more aggressive features and were at a more advanced stage than those in older patients. Precancerous lesions, such as atrophic gastritis and intestinal metaplasia, were observed less frequently in the older than in the younger group(P < 0.001). Molecular characteristics, including overexpression of p53(P < 0.001), overexpression of HER-2(P = 0.006), and MSI(P = 0.006), were less frequent in gastric cancer of younger patients. Cancer related mortality was higher in younger patients(P= 0.048), but this difference was not significant after adjusting for the stage of cancer.CONCLUSION: Gastric cancer is distinguishable between younger and older patients based on both clinicopathologic and molecular features, but stage is the most important predictor of prognosis.