Accurate staging of gastric cancer is helpful to determine the most appropriate therapy, but no staging modality has been accepted as the standard. Objective is to evaluate the usefulness of endoscopic ultrasonograph (EUS) combined with position emission tomography and computed tomograph (PET-CT) in gastric cancer staging. A total of 124 patients confirmed with gastric cancer were subjected to staging with EUS and PET-CT scanning. The detection rate of primary tumor was 99.2% by combination use of two modalities and 97.6% by EUS alone (p = 0.6219), but the detection rate was 90.3% (112 of 124) by PET-CT alone (compared with the combination, p = 0.0027; compared with EUS alone, p = 0.0299). The locoregional lymph node invasion was identified in 84/124 (67.7%) by combined PET-CT and EUS, which was obviously higher than that with EUS (52.4%) or PET-CT (43.5%) alone (p = 0.0194 and p = 0.0002, respectively). There was no statistical difference in identification of celiac axis lymph node metastasis among three methods, but the combined examination or PET-CT alone was more effective than EUS alone in the detection of distant metastases (all p < 0.01). Furthermore, the combined EUS and PET-CT was more optimal than using EUS or PET-CT alone in the accurate T and N staging and the effect on change of treatment. The present study indicates that the combination of EUS and PET-CT is an ideal modality in the preoperative staging of gastric cancer and it provides beneficial guidance for the treatment of gastric cancer.

Pancreatic adenocarcinoma (PC), one of the most fatal diseases, usually generates a poor prognosis in advanced stages. N6-methyladenosine modification has emerged as a crucial participant in tumor development and recurrence. Methyltransferase-like 14 (METTL14), as a core member of methyltransferases, is involved in tumor progression and metastasis. However, the potential mechanism by which METTL14 regulates long noncoding RNAs (lncRNAs) in PC remains unclear. RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), and fluorescence in situ hybridization (FISH) were used to explore the underlying mechanisms. In our study, we found that METTL14 expression was upregulated in PC patients, and was associated with poor prognosis. In vitro and in vivo experiments, knocking down METTL14 suppressed tumor metastasis. RNA-seq and bioinformatics analyses were used to identify LINC00941 as the downstream target of METTL14. Mechanistically, LINC00941 was upregulated by METTL14 in an m6A-dependent way. LINC00941 was recruited and recognized by IGF2BP2. METTL14 enhanced the affinity of IGF2BP2 for LINC00941, while IGF2BP2 promoted the stabilization of LINC00941, which contributed to the migration and invasion of PC cells. Overall, our research revealed that METTL14 promoted the metastasis of PC through m6A modification of LINC00941. Targeting the METTL14-LINC00941-IGF2BP2 axis may provide promising therapeutic approaches for PC.

Background: We conducted an assessment of 2'-O-methylated (2'OMe) microRNAs (miRNAs) present in the circulation of individuals suffering from pancreatic ductal adenocarcinoma (PDAC). Subsequently, we devised a set of circulating 2'OMe miRNAs that can be utilized for the screening of PDAC patients within a group at increased risk.

Background/Aims: Although endoscopic metal biliary endoprosthesis (EMBE) is widely accepted as the most suitable drainage method for patients with unresectable malignant obstruction, uncontrolled post-procedural cholangitis is still a problem. We aimed to validate a new treatment modality to prevent post-ERCP cholangitis in patients with unresectable cholangiocarcinoma. Patients and Methods: A total of 378 patients who were diagnosed with unresectable malignant biliary obstruction and underwent EMBE or temporary endoscopic nasobiliary drainage (ENBD) following EMBE placement, from January 2010 to July 2016, were enrolled in this retrospective study. Incidence of cholangitis, related infectious indicators, success rate of biliary drainage, and occurrence of complications were evaluated. Results: The risk of overall cholangitis and related infectious indicators was significantly lower in EMBE plus ENBD group than that in EMBE group. The occurrence of cholangitis was 2.4% versus 11.9% (P = 0.004). On further analysis of subgroups, although no difference was detected in nonhilar cholangiocarcinoma subgroup, the incidence of cholangitis and related infectious indicators in hilar cholangiocarcinoma subgroup with EMBE modality were distinctly higher than that with EMBE plus ENBD modality (type I + II was 18.5% vs 0%, P < 0.05; type III + IV was 19.8% vs 3.8%, P < 0.05). No significant difference was found in successful biliary drainage rate and procedure-related complications when all subgroups were compared. Conclusions: The temporary placement of ENBD following EMBE is a simple and effective treatment modality to prevent post-ERCP cholangitis, especially in patients with hilar cholangiocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a poor prognosis. Recently, necroptosis has been reported to participate in the progression of multiple tumors. However, few studies have revealed the relationship between necroptosis and PDAC, and the role of necroptosis in PDAC has not yet been clarified.Methods: The mRNA expression data and corresponding clinical information of PDAC patients were downloaded from the TCGA and GEO databases. The necroptosis-related genes (NRGs) were obtained from the CUSABIO website. Consensus clustering was performed to divide PDAC patients into two clusters. Univariate and LASSO Cox regression analyses were applied to screen the NRGs related to prognosis to construct the prognostic model. The predictive value of the prognostic model was evaluated by Kaplan-Meier survival analysis and ROC curve. Univariate and multivariate Cox regression analyses were used to evaluate whether the risk score could be used as an independent predictor of PDAC prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment analysis (ssGSEA) were used for functional enrichment analysis. Finally, using qRT-PCR examined NRGs mRNA expression in vitro.Results: Based on the TCGA database, a total of 22 differential expressed NRGs were identified, among which eight NRGs (CAPN2, CHMP4C, PLA2G4F, PYGB, BCL2, JAK3, PLA2G4C and STAT4) that may be related to prognosis were screened by univariate Cox regression analysis. And CAPN2, CHMP4C, PLA2G4C and STAT4 were further selected to construct the prognostic model. Kaplan-Meier survival analysis and ROC curve showed that there was a significant correlation between the risk model and prognosis. Univariate and multivariate Cox regression analyses showed that the risk score of the prognostic model could be used as an independent predictor. The model efficacy was further demonstrated in the GEO cohort. Functional analysis revealed that there were significant differences in immune status between high and low-risk groups. Finally, the qRT-PCR results revealed a similar dysregulation of NRGs in PDAC cell lines.Conclusion: This study successfully constructed and verified a prognostic model based on NRGs, which has a good predictive value for the prognosis of PDAC patients.

Inflammation is one of the inducing factors of pancreatic ductal adenocarcinoma (PDAC), and microRNAs have been confirmed to be involved in the occurrence and development of PDAC. However, whether RELA, an inflammatory regulator, is involved in the regulation of PDAC by miRNA remains to be further studied. In the present study miR-21 was characterized and its upstream regulatory mechanism was investigated, as well as its functional effects and target genes in pancreatic ductal adenocarcinoma (PDAC). In situ hybridization analysis confirmed increased miR-21 expression levels in PDAC tissues. The results of the chromatin immunoprecipitation and dual-luciferase reporter assays demonstrated that transcription factor RELA modulated miR-21 transcription in the PDAC, PANC-1 and MIA PaCa-2 cell lines. Subsequently, a cell viability assay, EdU staining assay and flow cytometry analysis, demonstrated that miR-21 promoted cell proliferation and cell cycle progression, but inhibited cell apoptosis in vitro. Furthermore, a xenograft assay demonstrated that miR-21 accelerated tumor growth in vivo. Mechanistically, miR-21 directly regulated the expression of Rho GTPase activating protein 24 (ARHGAP24), which was indicated to be a tumor suppressor gene. Moreover, both miR-21 and ARHGAP24 were strongly associated with clinical features and may therefore serve as valuable biomarkers in PDAC prognosis.