Progression Of Gastric Precancerous Lesions Research Articles

Rps3 Attenuates Gastric Precancerous Lesions by Promoting Dendritic Cells Maturation via AKT/β-Catenin Pathway.

This study aimed to investigate the dysregulated proteins and the underlying mechanisms of gastric precancerous lesions. Proteomic and phosphoproteomic methods were used to characterize the proteome and phosphoproteome profiles of N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced gastric precancerous lesions. The hub differentially expressed proteins (DEPs) and phosphoproteins (DEPPs) were identified by using differential expression and protein-protein interaction network analyses. Western blot assay, quantitative reverse transcription (qRT)-PCR, and CCK-8 assays detected the expression of Rps3, N-cadherin, E-cadherin, AKT, p-AKT, and β-catenin and verified the roles of Rps3 on the MNNG-induced human gastric epithelial cell line (GES-1) cells. Hub DEPs and phosphoproteins Rps3, Akt1, and Ctnnb1 were significantly correlated with five dendritic cells (DCs) pathways, and Akt1 and Ctnnb1 were significantly negatively correlated with Rps3. MNNG administration markedly reduced the Rps3 mRNA and protein expression levels (all P < 0.05). Overexpression of Rps3 significantly inhibited tumorigenesis of MNNG-induced GES-1 cells (all P < 0.01) and changed the protein levels of N-cadherin, E-cadherin, AKT, p-AKT, and β-catenin. Similarly, SC79 treatment substantially increased the expression of interleukin (IL)-6, IL-10, and vascular endothelial growth factor (all P < 0.05). Rps3 was poorly expressed in precancerous gastric lesions. Correspondingly, overexpression of Rps3 promoted DC maturation via the AKT/β-catenin pathway, inhibiting the progression of gastric precancerous lesions.

Histopathological and Immunohistochemical Mechanisms of Bone Marrow-Derived Mesenchymal Stem Cells in Reversion of Gastric Precancerous Lesions.

Gastric cancer (GC) stands as one of the most prevalent cancer types worldwide, holding the position of the second leading cause of cancer-related deaths. Gastric lesions represent pathological alterations to the gastric mucosa, with an elevated propensity to advance to gastric cancer. Limited research has explored the potential of stem cells in the treatment of gastric lesions. This study aimed to explore the potential of intravenous transplantation of labeled bone marrow-derived mesenchymal stem cells (BMMSCs) to inhibit the progression of precancerous gastric lesions. In the gastric lesion disease model group, the rat tissue exhibited noteworthy mucosal atrophy, intestinal metaplasia, dysplasia, and inflammatory cell infiltration. Following the infusion of BMMSCs, a notable decrease in gastric lesions was found, with atrophic gastritis being the sole remaining lesion, which was confirmed by morphological and histological examinations. BMMSCs that were colonized at gastric lesions could differentiate into epithelial and stromal cells, as determined by the expression of pan-keratin or vimentin. The expression of vascular endothelial growth factor was significantly elevated following BMMSC transplantation. BMMSCs could also upregulate the production of humoral immune response cytokines, including interleukin (IL)-4 and IL-10, and downregulate the production of IL-17 and interferon-gamma, which could be highly associated with the cellular immune response and inflammation severity of the lesions. BMMSC transplantation significantly reduced inflammation and reversed gastric lesion progression.

Effects of Helicobacter pylori and Moluodan on the Wnt/β-catenin signaling pathway in mice with precancerous gastric cancer lesions.

Helicobacter pylori (H. pylori) is the primary risk factor for gastric cancer (GC), the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis. GC has a high mortality rate and treatment cost, and there are no drugs to prevent the progression of gastric precancerous lesions to GC. Therefore, it is necessary to find a novel drug that is inexpensive and preventive to against GC. To explore the effects of H. pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC (PLGC). Mice were divided into the control, N-methyl-N-nitrosourea (MNU), H. pylori + MNU, and Moluodan groups. We first created an H. pylori infection model in the H. pylori + MNU and Moluodan groups. A PLGC model was created in the remaining three groups except for the control group. Moluodan was fed to mice in the Moloudan group ad libitum. The general condition of mice were observed during the whole experiment period. Gastric tissues of mice were grossly and microscopically examined. Through quantitative real-time PCR (qRT-PCR) and Western blotting analysis, the expression of relevant genes were detected. Mice in the H. pylori + MNU group showed the worst performance in general condition, gastric tissue visual and microscopic observation, followed by the MNU group, Moluodan group and the control group. QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes, the results showed that the H. pylori + MNU group had the highest expression, followed by the MNU group, Moluodan group and the control group. H. pylori can activate the Wnt/β-catenin signaling pathway, thereby facilitating the development and progression of PLGC. Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway, thereby decreasing the progression of PLGC.

Healthy plant-based diet might be inversely associated with gastric precancerous lesions: new evidence from a case-control study based on dietary pattern and fecal metabolic profiling

Preventing the progression of gastric precancerous lesions (GPLs) can reduce the morbidity and mortality of gastric cancer (GC). The preventive effect of a plant-based diet on cancers has been widely recognised. In this case–control study, 1,130 subjects were included using 1:1 propensity score matching for age and sex. Dietary habits, anthropometry and sample collection were conducted using standard and effective methods. Plant-based diet indices (PDIs) were calculated using a previously reported method. Faecal samples were analysed by untargeted metabolomics. Our study found that adherence to a healthy plant-based diet was inversely associated with the occurrence of GPLs. Metabolomic analysis identified six different metabolites correlated with GPLs, among which luteolin-related metabolites may be used as biomarkers of the association between PDIs and GPLs. In addition, the difference in N-acyl amides found in PDIs needs further verification. Our findings suggest that a healthy plant-based diet may have a protective effect against GPLs.

Gastric precancerous lesions:occurrence, development factors, and treatment.

Patients with gastric precancerous lesions (GPL) have a higher risk of gastric cancer (GC). However, the transformation of GPL into GC is an ongoing process that takes several years. At present, several factors including H.Pylori (Hp), flora imbalance, inflammatory factors, genetic variations, Claudin-4, gastric stem cells, solute carrier family member 26 (SLC26A9), bile reflux, exosomes, and miR-30a plays a considerable role in the transformation of GPL into GC. Moreover, timely intervention in the event of GPL can reduce the risk of GC. In clinical practice, GPL is mainly treated with endoscopy, acid suppression therapy, Hp eradication, a cyclooxygenase-2 inhibitor, aspirin, and diet. Currently, the use of traditional Chinese medicine (TCM) or combination with western medication to remove Hp and the use of TCM to treat GPL are common in Asia, particularly China, and have also demonstrated excellent clinical efficacy. This review thoroughly discussed the combining of TCM and Western therapy for the treatment of precancerous lesions as conditions allow. Consequently, this review also focuses on the causes of the development and progression of GPL, as well as its current treatment. This may help us understand GPL and related treatment.

Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta-analysis.

The question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta-analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions. PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random-effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses. Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81-0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17-1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69-0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30-2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15-1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37-2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47-1.70), Hp eradication had no advantage compared to placebo or no treatment. Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.

The expression and function of the B7 family in Helicobacter pylori infection and gastric carcinogenesis process.

The B7 protein family is one of the most important immune checkpoint proteins. Gastric cancer (GC) is the fourth most common cause of cancer-related mortality worldwide and shows a significant correlation with the B7 family in tumorigenesis and progression. Helicobacter pylori infection is the most important risk factor promoting the progression of gastric precancerous lesions and GC, which also affects the expression of B7 family members. We aimed to systematically summarize and review current studies on the expression and function of B7 family members during H. pylori infection in precancerous gastric lesions and GC. PubMed was searched for the relationship between B7 family, H. pylori and gastric carcinogenesis until April 5, 2023. Different permutation and combination of the search terms, including "H. pylori," "Helicobacter pylori," "B7," "gastric cancer," and "gastric precancerous lesions," all the different names of specific B7 molecules, and the names of signaling pathways were used. Literature related to our research topic was selected and summarized. The B7 family participates in gastric carcinogenesis through certain immune signaling pathways by binding to their receptors and exhibiting co-inhibitory or co-stimulatory effects. Targeting the B7 family members with mAbs may be a promising therapeutic strategy for treating gastric diseases. A thorough understanding of the role of B7 molecules during H. pylori infection and GC progression is helpful for the treatment and prevention of GC and the prediction of H. pylori infection outcomes, providing evidence for H. pylori eradication.

CagA and VacA inhibit gastric mucosal epithelial cell autophagy and promote the progression of gastric precancerous lesions.

Cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) are the keys to the pathogenic role of Helicobacter pylori and the high-risk factors for the progression of gastric precancerous lesions. Autophagy can stabilize the intracellular environment, resist Helicobacter pylori infection, prevent the accumulation of damaged DNA, and inhibit the proliferation of gastric precancerous variant cells. However, CagA and VacA can inhibit the activation of upstream signals of autophagy and the maturation of autophagy-lysosomes in various ways, thus inhibiting the autophagy of gastric mucosal cells in precancerous lesions of gastric cancer. This change can cause Helicobacter pylori to be unable to be effectively cleared by autophagy, so CagA and VacA can persist and promote the inflammation, oxidative stress, apoptosis of gastric mucosal tissue cells, and the glycolytic activity and proliferation of variant cells in gastric precancerous lesions and a series of malignant biological processes. In recent years, the research on drugs specifically inhibiting the activities of CagA and VacA has become a new direction for the prevention and treatment of Helicobacter pylori-related severe gastric diseases, and a variety of drugs or components that can precisely and effectively regulate the factors for the treatment of gastric precancerous lesions are emerged, which opens a new strategy for the treatment of gastric precancerous lesions in the future.

JAK-STAT1 Signaling Pathway Is an Early Response to Helicobacter pylori Infection and Contributes to Immune Escape and Gastric Carcinogenesis.

Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis and has been identified as a major risk factor for the development of gastric cancer (GC). Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling mediates immune regulatory processes, including tumor-driven immune escape. Programmed death ligand 1 (PD-L1) expressed on gastric epithelium can suppress the immune system by shutting down T cell effector function. In a human cohort of subjects with gastric lesions and GC analyzed by proteomics, STAT1 increased along the cascade of progression of precancerous gastric lesions to GC and was further associated with a poor prognosis of GC (Hazard Ratio (95% confidence interval): 2.34 (1.04–5.30)). We observed that STAT1 was activated in human H. pylori-positive gastritis, while in GC, STAT1, and its target gene, PD-L1, were significantly elevated. To confirm the dependency of H. pylori, we infected gastric epithelial cells in vitro and observed strong activation of STAT1 and upregulation of PD-L1, which depended on cytokines produced by immune cells. To investigate the correlation of immune infiltration with STAT1 activation and PD-L1 expression, we employed a mouse model of H. pylori-induced gastric lesions in an Rnf43-deficient background. Here, phosphorylated STAT1 and PD-L1 were correlated with immune infiltration and proliferation. STAT1 and PD-L1 were upregulated in gastric tumor tissues compared with normal tissues and were associated with immune infiltration and poor prognosis based on the TCGA-STAD database. H. pylori-induced activation of STAT1 and PD-L1 expression may prevent immune surveillance in the gastric mucosa, allowing premalignant lesions to progress to gastric cancer.

All-Trans Retinoic Acid Prevents the Progression of Gastric Precancerous Lesions by Regulating Disordered Retinoic Acid Metabolism

Retinoic acid (RA) is the most biologically active metabolite of vitamin A and is important for stomach physiological function. However, little is known about the metabolic status of RA in human gastric lesions. From 2015 to 2018, 1,392 local residents in Lujiang County were recruited into a cross-sectional survey program, which included a questionnaire interview and blood collection. We detected the mRNA and protein expression of RA metabolism-relevant factors in gastric tissues from 68 local patients with gastric lesions. The effects of all-trans retinoic acid (ATRA) supplementation were investigated in a gastric precancerous lesions (GPLs) rat model. In the cross-sectional survey, no significant differences in the level of RA precursor (P > 0.05) between the H. pylori seronegative and seropositive residents were observed. However, the mRNA and protein expression of RA synthesizing enzymes (RDH10 and ALDH1A1) were significantly decreased and catabolic enzyme (CYP26B1) was significantly increased in the patients (P < 0.05). Consistently, in the GPL rat model, we observed a similar disorder; however, ATRA supplementation significantly not only corrected the disorder by increasing Rdh10, Aldh1a1 and decreasing Cyp26b1, but also reduced claudin-18 (P < 0.05). Our study suggested that RA metabolism is disrupted in individuals with gastric lesions, while ATRA supplementation can prevent GPL from progressing to gastric cancer.

Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study.

Rationale: Gastric cancer (GC) is preceded by a stepwise progression of precancerous gastric lesions. Distinguishing individuals with precancerous gastric lesions that have progression potential to GC is an important need. Perturbated lipid metabolism, particularly the dysregulation of de novo lipogenesis, is involved in gastric carcinogenesis. We conducted the first prospective lipidomics study exploring lipidomic signatures for the risk of gastric lesion progression and early GC.Methods: Our two-stage study of targeted lipidomics enrolled 400 subjects from the National Upper Gastrointestinal Cancer Early Detection Program in China, including 200 subjects of GC and different gastric lesions in the discovery and validation stages. Of validation stage, 152 cases with gastric lesions were prospectively followed for the progression of gastric lesions for a median follow-up of 580 days (interquartile range 390-806 days). We examined the lipidomic signatures associated with the risk of advanced gastric lesions and their progression to GC. Our published tissue proteomic data were referred to further investigate highlighted lipids with their biologically related protein expression in gastric mucosa.Results: We identified 11 plasma lipids significantly inversely associated with the risk of gastric lesion progression and GC occurrence. These lipids were integrated as latent profiles to identify 5 clusters of lipid expression that had distinct risk of gastric lesion progression. The latent profiles significantly improved the ability to predict the progression potential of gastric lesions (AUC: 0.82 vs 0.68, Delong's P = 4.6×10-4) and risk of early GC (AUC: 0.81 vs 0.55, P = 6.3×10-5). Significant associations were found between highlighted lipids, their biologically correlated proteins and the risk of GC, supporting the role of the pathways involving monocarboxylic acid metabolism and lipid transport and catabolic process in GC.Conclusions: Our study revealed the lipidomic signatures associated with the risk of gastric lesion progression and GC occurrence, exhibiting translational implications for GC prevention.

Co-Exposure to Five Metals, Iron, Copper, Zinc, Selenium and Titanium, Prevents the Progression of Gastric Precancerous Lesions into Gastric Cancer

Co-Exposure to Five Metals, Iron, Copper, Zinc, Selenium and Titanium, Prevents the Progression of Gastric Precancerous Lesions into Gastric Cancer

Gastrointestinal Microbiota Changes in Patients With Gastric Precancerous Lesions.

BackgroundGastric microbiota may be involved in gastric cancer. The relationship between gastrointestinal microbes and the risk of gastric cancer is unclear. This study aimed to explore the gastric and intestinal bacteria associated with gastritis and gastric precancerous lesions. We conducted a case-control study by performing 16S rRNA gene analysis of gastric biopsies, juices, and stool samples from 148 cases with gastritis or gastric precancerous lesions from Anhui and neighboring provinces, China. And we validated our findings in public datasets.ResultsAnalysis of microbial sequences revealed decreased bacterial alpha diversity in gastric bacteria during the progression of gastritis. Helicobacter pylori was the main contributor to the decreased microbial composition and diversity in the gastric mucosa and had little influence on the microbiota of gastric juice and feces. The gastric mucosal genera Gemella, Veillonella, Streptococcus, Actinobacillus, and Hemophilus had the higher degree of centrality across the progression of gastric precancerous lesions. And Acinetobacter may contribute to the occurrence of intraepithelial neoplasia. In addition, the microbial model of H. pylori-positive gastric biopsies and feces showed value in the prediction of gastric precancerous lesions.ConclusionsThis study identified associations between gastric precancerous lesions and gastric microbiota, as well as the changes in intestinal microbiota, and explored their values in the prediction of gastric precancerous lesions.

Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

BackgroundMolecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management.MethodsWe portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280–473 days), and an independent case-control study from Beijing (n = 99).FindingsThere was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78–0.99) vs. 0.56 (0.36–0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins.InterpretationWe defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention.FundingThe funders are listed in the Acknowledgement.

Ginsenoside Rb1 Lessens Gastric Precancerous Lesions by Interfering With β-Catenin/TCF4 Interaction.

Background: Seeking novel and effective therapies for gastric precancerous lesions (GPL) is crucial to reducing the incidence of gastric cancer. Ginsenoside Rb1 (GRb1) is a major ginsenoside in ginseng and has been proved to possess multiple bioactivities. However, whether GRb1 could protect against GPL and the underlying mechanisms have not been explored.Methods: We evaluated the effects of GRb1 on gastric precancerous lesions in rats on macroscopic, microscopic and ultramicroscopic levels. Then, an antibody array was employed to screen differential expression proteins (DEPs). Validation for the targeting DEP and investigation for the possible mechanism was conducted using immunohistochemistry, qRT-PCR, TUNEL apoptosis assay, immunoprecipitation and immunoblotting.Results: GRb1 was found to reverse intestinal metaplasia and a portion of dysplasia in the MNNG-induced GPL rats. The antibody array assay revealed seven DEPs in GPL rats as compared to control rats (5 DEPs were up-regulated, while two DEPs were down-regulated). Among the DEPs, β-catenin, beta-NGF and FSTL1 were significantly down-regulated after GRb1 administration. Our validation results revealed that enhanced protein expression and nuclear translocation of β-catenin were present in animal GPL samples. In addition, analysis of human gastric specimens demonstrated that β-catenin up-regulation and nuclear translocation were significantly associated with advanced GPL pathology. GRb1 intervention not only decreased protein expression and nuclear translocation of β-catenin, but interfered with β-catenin/TCF4 interaction. Along with this, declined transcriptional and protein expression levels of downstream target genes including c-myc, cyclin D1 and Birc5 were observed in GRb1-treated GPL rats.Conclusion: GRb1 is capable of preventing the occurrence and progression of GPL, which might be contributed by diminishing protein expression and nuclear translocation of β-catenin and interfering with β-catenin/TCF4 interaction.

MicroRNA-365 inhibits YAP through TLR4-mediated IRF3 phosphorylation and thereby alleviates gastric precancerous lesions

BackgroundGastric carcinoma (GC) is currently one of the most common malignant tumors of the digestive system, and gastric precancerous lesions play a vital role in studying the mechanism of GC. Multiple microRNAs (miRNAs) have been documented to be potential biomarkers to indicate progression of gastric precancerous lesions. In this study, we explained the anti-cancer effect of miR-365 in gastric precancerous lesions via regulation of the TLR4/IRF3/YAP/CDX2 axis.MethodsmiR-365, TLR4, CDX2 and IPF3 expression was determined in GC and atrophic gastritis tissues and cells. After transfection of shRNA and overexpression plasmids, in vitro experiments detected the alteration of cell viability, apoptosis and inflammatory factors. Bioinformatics analysis, Co-IP and dual luciferase reporter gene assay were conducted to evaluate the binding between miR-365 and TLR4 as well as IRF3 and YAP. Rat models were established to explore the effect of the miR-365 and TLR4 on gastric precancerous lesions.ResultsmiR-365 was poorly expressed in GC and atrophic gastritis tissues and GC cell lines, while TLR4, CDX2 and IRF3 were overexpressed. Of note, miR-365 was indicated to target TLR4 and thereby suppressed cancer progression and increased hemoglobin content. Interestingly, silencing of TLR4 was accompanied by decreased IRF3 phosphorylation and reduced expression with less binding between CDX2 and IRF3. Downregulation of YAP resulted in declined CDX2 expression in cancer cells. Moreover, the inhibitory role of miR-365 was further confirmed in animal models.ConclusionTaken together, miR-365-mediated TLR4 inhibition reduces IRF3 phosphorylation and YAP-mediated CDX2 transcription to impede progression of gastric precancerous lesions.

Evaluation of a Phone Call Reminder Strategy in the Surveillance of Patients with Gastric Precancerous Lesions Lost to Follow-Up

Background: Surveillance of gastric precancerous lesions (GPL) may reduce gastric cancer (GC)-related mortality, but some patients with GPL are lost to follow-up. Objective: The aim of this study was to evaluate the feasibility and efficacy of a “phone-call” strategy in surveillance of the lost to follow-up patients. Patients and Methods: Among all the patients diagnosed with GPL (atrophic gastritis, intestinal metaplasia, low-grade dysplasia) between 2000 and 2015, we identified those who should undergo surveillance endoscopy according to the current guidelines. They were contacted by telephone and invited to undergo endoscopy with gastric biopsies for histological analysis. Results: Among 535 patients with GPL, 134 were contacted. Sixty-two (46%) could not be joined, 36 did not have endoscopy for other reasons, and finally, 36 patients (22 males, median age 65 years) were included. After the median time interval of 57 months between 2 endoscopies, 18 patients showed stability, 11 regression, and 7 progression of GPL, including 1 patient who developed GC. Conclusion: Despite several telephone calls, only one-third of the contacted patients could be brought to surveillance endoscopy. Most of the patients showed stability of GPL, but 1 progressed to GC and could be successfully treated.

Dynamic changes of Sonic Hedgehog signaling pathway in gastric mucosa of rats with MNNG-induced gastric precancerous lesions.

To explore the changes of Sonic Hedgehog (Shh) signaling pathway in the stomach mucosa during the formation of gastric precancerous lesions. A total of 72 suckling rats in half genders were randomly and equally divided into the normal group and model group. The rats in the model group were administered with 0.1 ml 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) at the dosage of 800 mg/L for 10 days, whereas the rats in the normal group were similarly administered with normal saline. A total of 12 rats in each group were killed at the end of 10th, 22nd, and 34th weeks in half gender, respectively. Histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (HE) staining; the levels of Shh, Ptch1, Smo, Gli1, Gli2, Gli3, SuFu, Cyclin D1, Cyclin E1, c-Myc, and β-actin mRNAs in the gastric mucosa were determined by real-time polymerase chain reaction; while the protein expression of Shh, Ptch1, Smo, Gli1, SuFu, Cyclin D1, Cyclin E1, c-Myc, and p-c-Myc was detected by western blot analysis. With the development of atrophy and dysplasia of gastric mucosa, the levels of Shh, Smo, Gli1, Cyclin D1, Cyclin E1, and c-Myc mRNAs increased, while those of Ptch1 and SuFu decreased. The expression of Shh, Smo, Gli1, Cyclin D1, Cyclin E1, and p-c-Myc proteins were elevated, while the expression of Ptch1 and SuFu proteins were decreased, however, without statistical difference. Shh signaling is activated during the formation of gastric precancerous lesions, which indicates that the Shh signaling pathway participates in the development and progression of gastric precancerous lesions.

Circulating microRNA-22-3p Predicts the Malignant Progression of Precancerous Gastric Lesions from Intestinal Metaplasia to Early Adenocarcinoma.

Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction. Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer. Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue. Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all P values < 0.05). Circulating miRNA-22-3p could be a potential biomarker for gastric precancerous dysplasia and early cancer detection.

Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial

ObjectiveTo evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions.Design795 adults with precancerous gastric lesions were randomised to receive anti-H. pylori...