Microbiome changes in the gastric mucosa and gastric juice in different histological stages of Helicobacter pylori-negative gastric cancers

BACKGROUND The gastric microbiota in patients with gastric cancer(GC)has received increasing attention,but the profiling of the gastric microbiome through the histological stages of gastric tumorigenesis remains poorly understood,especially for patients with Helicobacter pylori-negative GC(HPNGC).AIM To characterize microbial profiles of gastric mucosa and juice for HPNGC carcinogenesis and identify distinct taxa in precancerous lesions.METHODS The 16S rRNA gene analysis was performed on gastric mucosa from 134 Helicobacter pylori-negative cases,including 56 superficial gastritis(SG),9 atrophic gastritis(AG),27 intestinal metaplasia(IM),29 dysplasia(Dys),and 13 GC cases,to investigate differences in gastric microbial diversity and composition across the disease stages.In addition,paired gastric mucosa and juice samples from 18 SG,18 IM,and 18 Dys samples were analyzed.α-Diversity was measured by Shannon and Chao1 indexes,andβ-diversity was calculated using partial least squares discrimination analysis(PLS-DA).Differences in the microbial composition across disease stages in different sample types were assessed using the linear discriminant analysis effect size.RESULTS The diversity and composition of the bacterial microbiota in the gastric mucosa changed progressively across stages of gastric carcinogenesis.The diversity of the gastric mucosa microbiota was found to be significantly lower in the IM and Dys groups than in the SG group,and the patients with GC had the lowest bacterial community richness(P<0.05).Patients with IM and those with Dys had similar gastric mucosa microbiota profiles with Ralstonia and Rhodococcus as the predominant genera.Microbial network analysis showed that there was increasing correlation strength between IM and Dys(|correlation threshold|≥0.5,P<0.05).GC and its precancerous lesions have distinguishable bacterial taxa;our results identified HPNGC-associated bacteria Streptococcaceae and Lactobacillaceae(P<0.05).Additionally,across precancerous lesion stages from AG to Dys in Helicobacter pylori-negative patients,Burkholderiaceae abundance continuously increased,while Streptococcaceae and Prevotellaceae abundance presented a continuous downward trend.Furthermore,the microbial diversity was higher in gastric juice(P<0.001)than in the mucosa,while PLS-DA revealed a statistically significant difference between the two groups(ANOSIM,P=0.001).A significant difference in the microbial structure was identified,with Proteobacteria being more prevalent in the gastric mucosa and Firmicutes being more abundant in gastric juice.CONCLUSION Our results provide insights into potential taxonomic biomarkers for HPNGC and its precancerous stages and assist in predicting the prognosis of IM and Dys based on the mucosal microbiota profile.

Diagnostic value of serum human epididymis protein 4 in esophageal squamous cell carcinoma

BACKGROUND Numerous studies have demonstrated that human epididymis protein 4(HE4)is overexpressed in various malignant tissues including ovarian,endometrial,lung,breast,pancreatic,and gastric cancers.However,no study has examined the diagnostic impact of HE4 in patient with esophageal squamous cell carcinoma(ESCC)until now.AIM To analyze the value of four serum tumor markers for the diagnosis of ESCC,and examine the associations of serum levels of HE4 with ESCC patients’clinicopathological characteristics.METHODS The case group consisted of 80 ESCC patients,which were compared to a control group of 56 patients with benign esophageal disease.Serum levels of HE4,carcinoma embryonic antigen(CEA),alpha fetal protein,and carbohydrate antigen 19-9(CA19-9)were detected by ELISA.The associations of serum HE4 levels with ESCC patients’clinicopathological characteristics such as gender,tumor location,and pathological stage were also examined after operation.RESULTS The result of ELISA showed that serum HE4 level was significantly higher in the patients with ESCC than in the controls,and the staining intensity was inversely correlated with the pathological T and N stages.Serum HE4 levels had a sensitivity of 66.2%and specificity of 78.6%when the cutoff value was set at 3.9 ng/mL.Moreover,the combined HE4 and CA19-9 increased the sensitivity to 83.33%,and interestingly,the combination of HE4 with CEA led to the most powerful sensitivity of 87.5%.Furthermore,A positive correlation was observed between HE4 serum levels and pathological T and N stages(P=0.0002 and 0.0017,respectively),but there was no correlation between HE4 serum levels and ESCC patient gender(P=0.4395)or tumor location(P=0.6777).CONCLUSION The results of this study suggest that detection of serum HE4 levels may be useful in auxiliary diagnosis and evaluation of the progression of ESCC.