The role of gastric mucins and mucin-related glycans in gastric cancers.

Gastric mucins serve as a protective barrier on the stomach's surface, protecting from external stimuli including gastric acid and gut microbiota. Their composition typically changes in response to the metaplastic sequence triggered by Helicobacter pylori infection. This alteration in gastric mucins is also observed in cases of gastric cancer, although the precise connection between mucin expressions and gastric carcinogenesis remains uncertain. This review first introduces the relationship between mucin expressions and gastric metaplasia or cancer observed in humans and mice. Additionally, we discuss potential pathogenic mechanisms of how aberrant mucins and their glycans affect gastric carcinogenesis. Finally, we summarize challenges to target tumor-specific glycans by utilizing lectin-drug conjugates that can bind to specific glycans. Understanding the correlation and mechanism between these mucin expressions and gastric carcinogenesis could pave the way for new strategies in gastric cancer treatment.

Discovering cancer stem-like molecule, nuclear factor I X, using spatial transcriptome in gastric cancer.

Gastric cancer (GC) is characterized by significant intratumoral heterogeneity, and stem cells are promising therapeutic targets. Despite advancements in spatial transcriptome analyses, unexplored targets for addressing cancer stemness remain unknown. This study aimed to identify Nuclear Factor IX (NFIX) as a critical regulator of cancer stemness in GC and evaluate its clinicopathological significance and function. Spatial transcriptome analysis of GC was conducted. The correlation between NFIX expression, clinicopathological factors, and prognosis was assessed using immunostaining in 127 GC cases. Functional analyses of cancer cell lines validated these findings. Spatial transcriptome analysis stratified GC tissues based on genetic profiles, identified CSC-like cells, and further refined the classification to identify and highlight the significance of NFIX, as validated by Monocle 3 and CytoTRACE analyses. Knockdown experiments in cancer cell lines have demonstrated the involvement of NFIX in cancer cell proliferation and kinase activity. This study underscores the role of spatial transcriptome analysis in refining GC tissue classification and identifying therapeutic targets, highlighting NFIX as a pivotal factor. NFIX expression is correlated with poor prognosis and drives GC progression, suggesting its potential as a novel therapeutic target for personalized GC therapies.

Kinesin Family Member B18 Is Related to Gastric Mucin Phenotype and Contributes to Gastric Cancer Progression by Regulating Epithelial-Mesenchymal Transition.

INTRODUCTION: Gastric cancer (GC) remains a common health concern worldwide and is the third leading cause of death in Japan. It can be broadly classified into gastric and intestinal mucin phenotypes using immunohistochemistry. We previously reported numerous associations of kinesin family member (KIF) genes and mucin phenotypes with GC. However, no previous studies have reported on the importance of KIF18B in GC using immunostaining. Thus, in this study, we investigated the expression and functions of KIF18B, which is highly expressed in gastric mucin phenotype GC. METHODS: We performed RNA-seq of gastric and intestinal mucin type GCs, and clinicopathological studies of the KIF18B we found were performed using 96 GC cases. We also performed functional analysis using GC-derived cell lines. RESULT: RNA-seq showed the upregulation of matrisome-associated genes in gastric mucin phenotype GC and a high expression of KIF18B. KIF18B was detected in 52 of the 96 GC cases (54%) through immunohistochemistry. Low KIF18B expression was significantly associated with poor overall survival (p < 0.01). Other molecules that were significantly associated with KIF18B were MUC5AC and claudin 18; these were also significantly associated with the gastric mucin phenotype. KIF18B small interfering RNA (siRNA)-transfected GC cells showed greater growth and spheroid colony formation than the negative control siRNA-transfected cells. Furthermore, expression of snail family transcriptional repressor 1 and cadherin 2 was significantly increased and that of cadherin 1 was significantly decreased in KIF18B siRNA-transfected GC cells. CONCLUSION: These findings not only suggest that KIF18B may be a useful prognostic marker, but also provide insight into the pathogenesis of the GC phenotype.

A survival comparison of gastric mucin-producing adenocarcinoma to conventional adenocarcinoma: a SEER database analysis.

BACKGROUND: Compared to conventional adenocarcinoma (CA), mucin-producing adenocarcinoma (MPA) is an uncommon histological subtype and is usually separated from other histological types and has been evaluated separately. The objective was to compare the clinicopathological characteristics and survivals of MPA with CA. METHODS: We retrospectively analyzed 1515 MPA patients in SEER database. Log-rank tests and KM survival curves were applied to determine the differences in overall survival (OS) and cancer specific survival (CSS) time. RESULTS: No significant differences were noted in OS and CSS time. The MPA patients who were treated with surgery and chemotherapy exhibited longer OS and CSS time periods than those without treatment. MPA patients treated with radiotherapy exhibited similar OS and CSS time with those without radiotherapy. MPA was not a prognostic factor of survival. CONCLUSIONS: MPA was a rare histological type of gastric cancer. Patients with MPA exhibited similar prognosis with those with CA. Surgery and chemotherapy were effective treatments for patients with MPA.

Interactions of ß-Lactoglobulin with Bovine Submaxillary Mucin vs. Porcine Gastric Mucin: The Role of Hydrophobic and Hydrophilic Residues as Studied by Fluorescence Spectroscopy.

The aim of this study was to investigate binding interactions between ß-lactoglobulin (BLG) and two different mucins, bovine submaxillary mucins (BSM) and porcine gastric mucin (PGM), using intrinsic and extrinsic fluorescence spectroscopies. Intrinsic fluorescence spectra showed an enhanced decrease of fluorescence intensity of BLG at all pH conditions when BLG was mixed with PGM rather than with BSM. We propose that, unlike BSM, the tertiary structure of PGM changes and the hydrophobic regions are exposed at pH 3 due to protonation of negatively charged residues. Results suggest that PGM also facilitated the structural unfolding of BLG and its binding with PGM by a hydrophobic interaction, especially at acidic pH, which was further supported by extrinsic fluorescence spectroscopy. Hydrophobic interaction is suggested as the dominant interaction mechanism between BLG and PGM at pH 3, whereas electrostatic interaction is the dominant one between BLG and BSM.

Porcine Gastric Mucin Triggers Toxin Production of Enteropathogenic Bacillus cereus.

Enteropathogenic Bacillus cereus causes foodborne infections due to the production of pore-forming enterotoxins in the intestine. Before that, spores have to be ingested, survive the stomach passage, and germinate. Thus, before reaching epithelial cells, B. cereus comes in contact with the intestinal mucus layer. In the present study, different aspects of this interaction were analyzed. Total RNA sequencing revealed major transcriptional changes of B. cereus strain F837/76 upon incubation with porcine gastric mucin (PGM), comprising genes encoding enterotoxins and further putative virulence factors, as well as proteins involved in adhesion to and degradation of mucin. Indeed, PGM was partially degraded by B. cereus via secreted, EDTA-sensitive proteases. The amount of enterotoxins detectable in culture media supplemented with PGM was also clearly increased. Tests of further strains revealed that enhancement of enterotoxin production upon contact with PGM is broadly distributed among B. cereus strains. Interestingly, evidence was found that PGM can also strain-specifically trigger germination of B. cereus spores and that vegetative cells actively move toward mucin. Overall, our data suggest that B. cereus is well adapted to the host environment due to massive transcriptome changes upon contact with PGM, attributing mucin an important and, thus far, neglected role in pathogenesis.

Clinical and Pathological Challenges in the Diagnosis of Gastric-Type Differentiated Adenocarcinoma in the Stomach: A Study of Endoscopic Submucosal Dissection Cases.

BACKGROUND/AIMS: Gastric-type differentiated adenocarcinoma (GDA) of the stomach is a rare variant of gastric cancer that is highly infiltrating and exhibits early metastasis. However, the endoscopic and pathological features of "early-stage" GDA remain unknown. The aim of this study is to characterize early-stage GDA. METHODS: We retrospectively enrolled 479 differentiated-type early gastric cancer cases who underwent endoscopic submucosal dissection (ESD). GDA cases were selected based on morphology and immunohistochemistry. Clinicopathological data were compared between gastric- and intestinal-type differentiated adenocarcinomas (IDAs). RESULTS: Thirteen lesions were classified as GDAs. GDAs as well as IDAs showed irregular microvascular and microsurface patterns with clear demarcation line on magnifying endoscopy with narrow band imaging (M-NBI). The rate of pathological misdiagnosis of GDAs in biopsy specimens was higher than that of IDAs (p = 0.016). GDA was significantly associated with positive lymphovascular invasion (p = 0.016). There was one intramucosal lesion with lymphatic invasion in GDA. CONCLUSIONS: Although M-NBI is useful to detect GDA, the pathological diagnosis of GDAs in biopsy specimens often remains challenging. When suspicious lesions are not diagnosed as GDA, they should be followed up intensively, or diagnostic ESD has to be performed. ESD specimens should be carefully evaluated because of a higher incidence of lymphovascular invasion.

Evaluation of porcine gastric mucin assay for detection and quantification of human norovirus in fresh herbs and leafy vegetables.

Leafy vegetables and fresh herbs are important parts of a healthy diet, however, they can be common vehicles of norovirus (NoV) infection and lead to serious health and economic concerns globally. NoV is highly infectious and persistent in the food and the environment, while being resistant to conventional food decontamination practices. Herbs and leafy greens are often consumed raw, and if contaminated with NoV, they may cause illness. Consequently, for outbreak prevention and surveillance purposes, sensitive and rapid methods are required to detect the presence of infectious NoV in naturally contaminated produce during its shelf life. Herein, we compared the extraction efficiency of the ISO/TS 15216-1:2017 method with the porcine gastric mucin coated magnetic beads (PGM-MB) assay, combined with heat-denaturation for RNA extraction, for detection of human NoV in artificially contaminated fresh green seaweed, basil, mint, and baby spinach. Droplet-digital RT-PCR was used to quantify the extracted genome by both methods. Our data demonstrated that while the PGM-MB assay takes considerably less time, it yields significantly higher recovery rates compared with the ISO/TS 15216-1:2017. Furthermore, since this method has the ability to be adapted in high-throughput and automated systems, it can be further modified to be employed by the food industry to reduce the number of NoV illnesses and outbreaks at the source of distribution.

Molecular Detection of H. pylori Using Adherent Gastric Mucous to Biopsy Forceps.

BACKGROUND AND AIM: We assessed whether adherent gastric mucous to biopsy forceps instead of biopsy samples was suitable for the diagnosis of H. pylori infection. We confirmed the PCR methods to improve the diagnosis of H. pylori infection and clarithromycin (CAM) susceptibility. METHODS: Gastric mucous was obtained by gently scraping gastric mucosa using biopsy forceps in patients undergoing upper gastrointestinal (GI) endoscopy for PCR and rapid urease test (RUT). DNA was extracted from gastric mucous present within the gel of RUT. H. pylori status and CAM susceptibility were evaluated using H. pylori-specific PCR amplification for 23S rRNA using 4 different primer sets and 16S rRNA. H. pylori positive was defined as two of the three tests (serum antibody, histology, and RUT or PCR) were positive. CAM susceptibility was evaluated by point mutations (A 2142G and A 2143G of 23S rRNA). RESULTS: Samples taken from 494 subjects were evaluated: 300 H. pylori-positive patients and 194 negative patients. The results of PCR using DNA extracted from gastric mucous present within the RUT gel were consistent with those within water. The accuracy of 23S rRNA PCR for H. pylori detection using RUT samples was superior to the other tests. The frequency of CAM resistance was 38.9%, and eradication rate was 91.3% in the patients with wild-type and 47.0% in the patients with the mutant strains. CONCLUSION: Adherent gastric mucous to biopsy forceps in RUT gel can be used for molecular testing to confirm the diagnosis of H. pylori infection and for CAM susceptibility.

Immunohistochemical Expressions of MUC2, MUC5AC, and MUC6 in Normal, Helicobacter pylori Infected and Metaplastic Gastric Mucosa of Children and Adolescents.

OBJECTIVES: The aim of this study was to investigate expression of gastric mucins in children and adolescents and to assess their relations with age and Helicobacter pylori (H. pylori) infection. METHODS: Gastric biopsies were collected from 259 pediatric and adulthood patients with gastrointestinal symptoms among all of patients undergone gastroduodenoscopy from 1990 to 2004 at Gyeongsang National University hospital and assorted based on H. pylori infection, age, and intestinal metaplasia as follows; H. pylori infection before 5 years of age or not, H. pylori infection between 5 and 9 years of age or not, H. pylori infection between 10 and 14 years of age or not, H. pylori infection between 20 and 29 years of age or not and intestinal metaplasia between 21 and 35 years of age. Total 810 tissue slides from the subjects were examined regarding expressions of Mucin2 (MUC2), Mucin5AC (MUC5AC), and Mucin6 (MUC6) in nine groups using immunohistochemical stains. A semiquantitative approach was used to score the staining extent of tissue slide. RESULTS: Increased expressions of MUC2, MUC5AC, and MUC6 were noted in intestinal metaplasia compared with subjects infected with H. pylori between 20 and 29 years. Gastric expressions of MUC5AC were decreased in older than 5 years with H. pylori compared with in older than 5 years without H. pylori (p < .001). Expressions of MUC2 and MUC6 did not change significantly by H. pylori status. Some nuclear expressions of MUC2 and MUC6 were noted in children without intestinal metaplasia. CONCLUSIONS: MUC5AC might be affected by chronic H. pylori infection. In addition to biomarkers for intestinal metaplasia or prognostic factors for gastric cancer in adults, MUC2 and MUC6 in children might have an another role, based on ectopic gastric nuclear expressions of MUC2 and MUC6 in children without intestinal metaplasia.

PPARα autocrine regulation of Ca²âº-regulated exocytosis in guinea pig antral mucous cells: NO and cGMP accumulation.

In antral mucous cells, acetylcholine (ACh, 1 µM) activates Ca(2+)-regulated exocytosis, consisting of a peak in exocytotic events that declines rapidly (initial phase) followed by a second slower decline (late phase) lasting during ACh stimulation. GW7647 [a peroxisome proliferation activation receptor α (PPARα) agonist] enhanced the ACh-stimulated initial phase, and GW6471 (a PPARα antagonist) abolished the GW7647-induced enhancement. However, GW6471 produced the delayed, but transient, increase in the ACh-stimulated late phase, and it also decreased the initial phase and produced the delayed increase in the late phase during stimulation with ACh alone. A similar delayed increase in the ACh-stimulated late phase is induced by an inhibitor of the PKG, Rp8BrPETcGMPS, suggesting that GW6471 inhibits cGMP accumulation. An inhibitor of nitric oxide synthase 1 (NOS1), N(5)-[imino(propylamino)methyl]-L-ornithine hydrochloride (N-PLA), also abolished the GW7647-induced-enhancement of ACh-stimulated initial phase but produced the delayed increase in the late phase. However, in the presence of N-PLA, an NO donor or 8BrcGMP enhanced the ACh-stimulated initial phase and abolished the delayed increase in the late phase. Moreover, GW7647 and ACh stimulated NO production and cGMP accumulation in antral mucosae, which was inhibited by GW6471 or N-PLA. Western blotting and immunohistochemistry revealed that NOS1 and PPARα colocalize in antral mucous cells. In conclusion, during ACh stimulation, a PPARα autocrine mechanism, which accumulates NO via NOS1 leading to cGMP accumulation, modulates the Ca(2+)-regulated exocytosis in antral mucous cells.

Measurement of Mucinase Activity.

Mucinase consists of some proteases, glycosidases, sulfatases, and sialidases. It is not practical to measure individual enzyme activities when measuring mucinase activity. In this method, mucinase activity is measured using porcine gastric mucin as a substrate and feces as an enzyme source. This description includes fecal pellet preparation, reaction procedure of mucinase, measurement of reducing sugars liberated during the procedure, and determination of nitrogen content in the fecal preparations.

Extraction and Fractionation of Human Gastric Mucins from Gastric Juice.

Mucin, a major component of the mucus, is considered to be one of the principal factors in the physiological defense mechanism of the gastrointestinal mucosa. Measuring the mucin content of human gastric mucus is a useful tool for the assessment of Helicobacter pylori (H. pylori) eradication or the involvement of mucus secretion in various gastroduodenal diseases. Here, we describe a methodology for the isolation of the mucin fraction from human gastric juice and the quantification of mucin.

Unraveling the Intertwined Effect of pH on Helicobacter pylori Motility and the Microrheology of the Mucin-Based Medium It Swims in.

The gastric pathogen, Helicobacter pylori bacteria have to swim across a pH gradient from 2 to 7 in the mucus layer to colonize the gastric epithelium. Previous studies from our group have shown that porcine gastric mucin (PGM) gels at an acidic pH < 4, and H. pylori bacteria are unable to swim in the gel, although their flagella rotate. Changing pH impacts both the rheological properties of gastric mucin and also influences the proton (H+)-pumped flagellar motors of H. pylori as well as their anti-pH sensing receptors. To unravel these intertwined effects of acidic pH on both the viscoelastic properties of the mucin-based mucus as well as the flagellar motors and chemo-receptors of the bacterium, we compared the motility of H. pylori in PGM with that in Brucella broth (BB10) at different pH values using phase contrast microscopy to track the motion of the bacteria. The results show that the distribution of swimming speeds and other characteristics of the bacteria trajectories exhibit pH-dependent differences in both media. The swimming speed exhibits a peak at pH 4 in BB10, and a less pronounced peak at a higher pH of 5 in PGM. At all pH values, the bacteria swam faster and had a longer net displacement in BB10 compared to PGM. While the bacteria were stuck in PGM gels at pH < 4, they swam at these acidic pH values in BB10, although with reduced speed. Decreasing pH leads to a decreased fraction of motile bacteria, with a decreased contribution of the faster swimmers to the distributions of speeds and net displacement of trajectories. The body rotation rate is weakly dependent on pH in BB10, whereas in PGM bacteria that are immobilized in the low pH gel are capable of mechano-sensing and rotate faster. Bacteria can be stuck in the gel in various ways, including the flagella getting entangled in the fibers of the gel or the cell body being stuck to the gel. Our results show that in BB10, swimming is optimized at pH4, reflecting the combined effects of pH sensing by anti-pH tactic receptors and impact on H+ pumping of flagellar motors, while the increase in viscosity of PGM with decreasing pH and gelation below pH 4 lead to further reduction in swimming speed, with optimal swimming at pH 5 and immobilization of bacteria below pH 4.

Gastric-type duodenal neoplasms with rapid growth: A report of two cases.

While duodenal neoplasms of the gastric phenotype are uncommon and their natural history is unknown, gastric neoplasms of gastric phenotype reportedly grow rapidly and can invade the submucosa. Several studies suggest that duodenal neoplasms of gastric phenotype might have a high risk of deep invasion and lymph node metastasis. Duodenal neoplasms of gastric phenotype might also have a high biological malignancy and likely require early treatment if detected. Here, we report two cases of intramucosal duodenal carcinoma with a gastric phenotype that grew rapidly but was successfully resected endoscopically.

Motility of Different Gastric Helicobacter spp.

Helicobacter spp., including the well-known human gastric pathogen H. pylori, can cause gastric diseases in humans and other mammals. They are Gram-negative bacteria that colonize the gastric epithelium and use their multiple flagella to move across the protective gastric mucus layer. The flagella of different Helicobacter spp. vary in their location and number. This review focuses on the swimming characteristics of different species with different flagellar architectures and cell shapes. All Helicobacter spp. use a run-reverse-reorient mechanism to swim in aqueous solutions, as well as in gastric mucin. Comparisons of different strains and mutants of H. pylori varying in cell shape and the number of flagella show that their swimming speed increases with an increasing number of flagella and is somewhat enhanced with a helical cell body shape. The swimming mechanism of H. suis, which has bipolar flagella, is more complex than that of unipolar H. pylori. H. suis exhibits multiple modes of flagellar orientation while swimming. The pH-dependent viscosity and gelation of gastric mucin significantly impact the motility of Helicobacter spp. In the absence of urea, these bacteria do not swim in mucin gel at pH < 4, even though their flagellar bundle rotates.

Complexation between porcine gastric mucin (PGM) and lysozyme: Influence of heat treatment of lysozyme on the tribological properties.

The influence of complexation between porcine gastric mucin (PGM) and lysozyme (LYZ) solutions (pH⁓7.0) on their lubricating properties was studied at a hydrophobic self-mated polydimethylsiloxane (PDMS) tribopair. To this end, LYZ solutions with varying heating time, namely 1hr, 3hr-, and 6hr at 90 °C, as well as unheated LYZ solution, were prepared. The lubricating capability of PGM and LYZ solutions and also their mixtures was characterized using pin-on-disk tribometry. In parallel, to precisely investigate the interaction between PGM and LYZ solutions, an array of the well-known experiments including electrophoretic-dynamic light scattering, circular dichroism spectroscopy and optical waveguide light-mode spectroscopy were employed. These experiments were utilized to elucidate the key features e.g. zeta potential, hydrodynamic diameter, conformational structure and mass adsorption. The tribometry results indicated that both PGM and unheated LYZ solutions had poor lubricating properties in the boundary lubrication regime (sliding speed lower than 10 mm/s). Mixing PGM with unheated LYZ led to a slight decrease in the friction coefficient, but no desirable lubricity was observed. An optimum slippery characteristic was achieved by incorporating 1hr heated LYZ solution into PGM one. Excellent lubricity of PGM/1hr heated LYZ may stem from surface charge compensation, tenaciously compact aggregation, unique conformational structure and considerable mass adsorption onto PDMS. This finding revealed that a strong interaction between PGM and LYZ molecules and as a result, the promising lubricating capability of PGM/LYZ mixtures, can be administered by varying heat-treatment duration of LYZ proteins.

A novel approach to concentrate human and animal viruses from wastewater using receptors-conjugated magnetic beads.

Viruses are present at low concentrations in wastewater; therefore, an effective method for concentrating virus particles is necessary for accurate wastewater-based epidemiology (WBE). We designed a novel approach to concentrate human and animal viruses from wastewater using porcine gastric mucin-conjugated magnetic beads (PGM-MBs). We systematically evaluated the performances of the PGM-MBs method (sensitivity, specificity, and robustness to environmental inhibitors) with six viral species, including Tulane virus (a surrogate for human norovirus), rotavirus, adenovirus, porcine coronavirus (transmissible gastroenteritis virus or TGEV), and two human coronaviruses (NL63 and SARS-CoV-2) in influent wastewater and raw sewage samples. We determined the multiplication factor (the ratio of genome concentration of the final solution to that of the initial solution) for the PGM-MBs method, which ranged from 1.3 to 64.0 depending on the viral species. Because the recovery efficiency was significantly higher when calculated with virus titers than it was with genome concentration, the PGM-MBs method could be an appropriate tool for assessing the risk to humans who are inadvertently exposed to wastewater contaminated with infectious viruses. Furthermore, PCR inhibitors were not concentrated by PGM-MBs, suggesting that this tool will be successful for use with environmental samples. In addition, the PGM-MBs method is cost-effective (0.5 USD/sample) and has a fast turnaround time (3 h from virus concentration to genome quantification). Thus, this method can be implemented in high throughput facilities. Because of its strong performance, intrinsic characteristics of targeting the infectious virus, robustness to wastewater, and adaptability to high throughput systems, the PGM-MBs method can be successfully applied to WBE and ultimately provides valuable public health information.

Double-Cross-Linked Networks Based on Methacryloyl Mucin.

Mucin is a glycoprotein with proven potential in the biomaterials field, but its use is still underexploited for such applications. The present work aims to produce a synthesis of methacryloyl mucin single-network (SN) hydrogels and their double-cross-linked-network (DCN) counterparts. Following the synthesis of the mucin methacryloyl derivative, various SN hydrogels are prepared through the photopolymerization of methacrylate bonds, using reaction media with different pH values. The SN hydrogels are converted into DCN systems via supplementary cross-linking in tannic acid aqueous solution. The chemical modification of mucin is described, and the obtained product is characterized; the structural modification of mucin is assessed through FTIR spectroscopy, and the circular dichroism and the isoelectric point of methacryloyl mucin is evaluated. The affinity for aqueous media of both SN and DCN hydrogels is estimated, and the mechanical properties of the systems are assessed, both at macroscale through uniaxial compression and rheology tests and also at microscale through nanoindentation tests.

Gastric mucin phenotype indicates aggressive biological behaviour in early differentiated gastric adenocarcinomas following endoscopic treatment.

BACKGROUND: The distribution of mucin phenotypes and their relationship with clinicopathological features in early differentiated gastric adenocarcinomas in a Chinese cohort are unknown. We aimed to investigate mucin phenotypes and analyse the relationship between mucin phenotypes and clinicopathological features, especially biological behaviours, in early differentiated gastric adenocarcinomas from endoscopic specimens in a Chinese cohort. METHODS: Immunohistochemical staining of CD10, MUC2, MUC5AC, and MUC6 was performed in 257 tissue samples from patients with early differentiated gastric adenocarcinomas. The tumour location, gross type, tumour size, histological type, depth of invasion, lymphovascular invasion, mucosal background and other clinicopathological parameters were evaluated. The relationship between mucin phenotypes and clinicopathological features was analysed with the chi-square test. RESULTS: The incidences of gastric, gastrointestinal, intestinal and null phenotypes were 21 %, 56 %, 20 and 3 %, respectively. The mucin phenotypes were related to histology classification (P < 0.05). The proportion of the gastric phenotype became greater during the transition from differentiated to undifferentiated (P < 0.05). Complete intestinal metaplasia was higher in the gastric and intestinal phenotypes than in the gastrointestinal phenotype (P < 0.05). Tumours with poorly differentiated adenocarcinoma were mainly of the gastric phenotype, which was significantly higher than that of purely differentiated tubular adenocarcinoma (P < 0.05), and the depth of invasion in the mixed type was deeper (P < 0.05). Neither recurrence nor metastasis was detected. CONCLUSIONS: The mucin phenotype of early-differentiated gastric adenocarcinoma has clinical implications, and the gastric phenotype has aggressive biological behaviour in early differentiated gastric cancers, especially in those with poorly differentiated adenocarcinoma or papillary adenocarcinoma components.