AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013. Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia (LGIN), 20 high-grade intraepithelial neoplasia (HGIN), 19 early-stage adenocarcinoma (EGC), and 19 chronic gastritis tissue samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology (GO) enrichment analysis was performed using the GeneSpring software GX 12.6. The differentially expressed gene was verified using a real-time TaqMan^® PCR assay with independent tissue samples, including 26 LGIN, 15 HGIN, 14 EGC, and 20 chronic gastritis. The expression of G₀S₂ were further validated by immunohistochemical staining (IHC) in 24 LGIN, 40 HGIN, 30 EGC and 61 chronic gastritis specimens. RESULTS: The gene expression patterns of LGIN and HGIN tissues were distinct. There were 2521 significantly differentially expressed transcripts in HGIN, with 951 upregulated and 1570 downregulated. A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism, defense response, and nuclear factor κB (NF-κB) cascade. While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues, only 38 transcripts were upregulated in EGC. A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC. It is worth noting that, compared with LGIN, 289 transcripts were expressed at higher levels both in HGIN and EGC. A characteristic gene, G₀/G₁ switch 2 (G₀S₂) was one of the 289 transcripts and related to metabolism, the immune response, and the NF-κB cascade, and its expression was validated in independent samples through real-time TaqMan^® PCR and immunohistochemical staining. In real-time PCR analysis, the expression of G₀S₂ was elevated both in HGIN and EGC compared with that in LGIN (P < 0.01 and P < 0.001, respectively). In IHC analysis, G₀S₂ immunoreactivity was detected in the cytoplasmic of neoplastic cells, but was undetectable in chronic gastritis cells. The G₀S₂ expression in HGIN was higher than that of LGIN (P = 0.012, χ² = 6.28) and EGC (P = 0.008, χ² = 6.94). CONCLUSION: A clear biological distinction between gastric high- and low-grade intraepithelial neoplasia was identified, and provides molecular evidence for clinical application.

Background: The gastric microbiota profile alters during gastric carcinogenesis. We aimed to identify the alterations in the alpha diversity and relative abundance of bacterial phyla and genera of gastric microbiota in the development of gastric cancer (GC).Methods: The systematic review was performed based on a published protocol with the registration number CRD42020206973. We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (May 2021) for observational studies reporting either the relative abundance of bacterial phyla or genera, or alpha diversity indexes in both GC and non-cancer groups. Selection of studies and data extraction were performed independently by two researchers, with disagreements resolved through discussion. Risk of bias was assessed using the self-modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD).Results: Our systematic review included 751 GC patients and 792 non-cancer patients from 14 case-control studies. Gastric cancer group had fewer operational taxonomic units (OTUs) (MD = −68.52, 95%CI: −126.65 to −10.39) and a lower Simpson index (MD = −0.13, 95%CI: −0.20 to −0.07) compared with non-cancer group. At the phylum level, gastric cancer group had a higher abundance of Firmicutes (MD = 7.11, 95%CI: 1.76 to 12.46). At the genus level, Streptococcus (MD = 3.03, 95%CI: 0.07 to 6.00) and Lactobacillus (MD = 5.15, 95%CI: 1.27 to 9.04) were found to be enriched in GCgroup. The relative abundance of the rest bacterial phyla or genera analyzed in our study did not significantly differ between two groups. Subgroup analyses indicated that the source of samples was the major source of interstudy heterogeneity.Conclusion: This systematic review suggested that gastric microbiota dysbiosis occurred in gastric carcinogenesis, with alpha diversity declined and microbiota composition altered.

As the most frequent functional pancreatic neuroendocrine tumor, insulinomas may cause a plethora of symptoms and severe impairment in the living of patients by endogenous hyperinsulinemia and subsequent hypoglycemia. Surgery has been regarded as the first choice although a high risk of complications. Ethanol ablation is a promising non-surgical option that could achieve tumor shrinking in a short-term period. But the impact of symptom control and the long-term efficacy lack sufficient and good-quality evidence. A total number of 14 endoscopic ultrasonography-guided ethanol ablations were performed in 9 patients between September 2016 and September 2018 in Peking Union Medical College Hospital. The data were collected and prospectively analyzed. The follow-up duration ranged from 21 to 1567 days in 9 patients, with a median of 994 days. 4 patients were free from relapse during a median follow-up of 1108 days (range: 994-1567 days). In 5 patients who suffered relapses, the median duration with symptom relief after the first ablation was 128 days (range: 13-393 days). If only repeated ablation was taken into consideration, the median duration with symptom relief was 26 days (range: 1-516 days). No complications happened during the procedures. The severe complication rate after the first ablation was 0.0% (0/9), compared to 7.14% (1/14) if each procedure was counted separately. The only severe complication documented was acute pancreatitis which was completely relieved after symptomatic treatment. For patients who are not suitable for surgical resections, endoscopic ultrasonography-guided ethanol ablation of insulinomas could be an effective and safe alternative to relieve symptoms of hypoglycemia.

Background. BRCA1 interacting helicase 1 (BRIP1), an ATP-dependent DNA helicase which belongs to an Iron-Sulfur (Fe-S) helicase cluster family with a DEAH domain, plays a key role in DNA damage and repair, Fanconi anemia, and development of several cancers including breast and ovarian cancer. However, its role in pan-cancer remains largely unknown. Methods. BRIP1 expression data of tumor and normal tissues were downloaded from the Cancer Genome Atlas, Genotype-Tissue Expression, and Human Protein Atlas databases. Correlation between BRIP1 and prognosis, genomic alterations, and copy number variation (CNV) as well as methylation in pan-cancer were further analyzed. Protein-protein interaction (PPI) and gene set enrichment and variation analysis (GSEA and GSVA) were performed to identify the potential pathways and functions of BRIP1. Besides, BRIP1 correlations with tumor microenvironment (TME), immune infiltration, immune-related genes, tumor mutation burden (TMB), microsatellite instability (MSI), and immunotherapy as well as antitumor drugs were explored in pan-cancer. Results. Differential analyses showed an increased expression of BRIP1 in 28 cancer types and its aberrant expression could be an indicator for prognosis in most cancers. Among the various mutation types of BRIP1 in pan-cancer, amplification was the most common type. BRIP1 expression had a significant correlation with CNV and DNA methylation in 23 tumor types and 16 tumor types, respectively. PPI, GSEA, and GSVA results validated the association between BRIP1 and DNA damage and repair, cell cycle, and metabolism. In addition, the expression of BRIP1 and its correlation with TME, immune-infiltrating cells, immune-related genes, TMB, and MSI as well as a variety of antitumor drugs and immunotherapy were confirmed. Conclusions. Our study indicates that BRIP1 plays an imperative role in the tumorigenesis and immunity of various tumors. It may not only serve as a diagnostic and prognostic biomarker but also can be a predictor for drug sensitivity and immunoreaction during antitumor treatment in pan-cancer.

Background and aims: Accurate evaluation of intraductal papillary mucinous neoplasm (IPMN) is necessary to inform clinical decision-making. But it is still difficult to distinguish benign and malignant IPMN preoperatively. This study aims to evaluate the utility of EUS to predict the pathology of IPMN. Methods: Patients with IPMN who underwent endoscopic ultrasound within 3 months before surgery were collected from six centers. Logistic regression model and random forest model were used to determine risk factors associated with malignant IPMN. In both models, 70% and 30% of patients were randomly assigned to the exploratory group and validation group, respectively. Sensitivity, specificity, and ROC were used in model assessment. Results: Of the 115 patients, 56 (48.7%) had low-grade dysplasia (LGD), 25 (21.7%) had high-grade dysplasia (HGD), and 34 (29.6%) had invasive cancer (IC). Smoking history (OR = 6.95, 95%CI: 1.98–24.44, p = 0.002), lymphadenopathy (OR = 7.91, 95%CI: 1.60–39.07, p = 0.011), MPD > 7 mm (OR = 4.75, 95%CI: 1.56–14.47, p = 0.006) and mural nodules > 5 mm (OR = 8.79, 95%CI: 2.40–32.24, p = 0.001) were independent risk factors predicting malignant IPMN according to the logistic regression model. The sensitivity, specificity, and AUC were 0.895, 0.571, and 0.795 in the validation group. In the random forest model, the sensitivity, specificity, and AUC were 0.722, 0.823, and 0.773, respectively. In patients with mural nodules, random forest model could reach a sensitivity of 0.905 and a specificity of 0.900. Conclusions: Using random forest model based on EUS data is effective to differentiate benign and malignant IPMN in this cohort, especially in patients with mural nodules.