Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.

Nicotinamide nucleotide transhydrogenase‐antisense RNA1 (NNT‐AS1) is a long noncoding RNA (lncRNA) that has been shown to be overexpressed in hepatocellular carcinoma (HCC). However, the molecular mechanism involving NNT‐AS1 in HCC remains to be extensively investigated. The activation of TGF‐β signaling inhibits tumor‐infiltrating lymphocytes (TILs) and results in tumor immune evasion. We thus planned to explore the mechanism by which NNT‐AS1 activates the TGF‐β signaling pathway and inhibits TILs in HCC. High levels of NNT‐AS1 were detected in HCC tissues by both RNAscope and real‐time quantitative PCR (RT‐qPCR) assays. The levels of proteins involved in TGF‐β signaling and those of CD4 T lymphocytes were quantified by immunohistochemistry (IHC). HCC cell lines (HepG2 and Huh7) were used to explore the effects of NNT‐AS1 on TGF‐β signaling activation. In these analyses, RNAscope detection demonstrated that NNT‐AS1 levels were significantly increased in HCC cancer tissues (P = 0.0001). In addition, the elevated NNT‐AS1 levels in cancer tissue were further confirmed by RT‐qPCR analysis of HCC cancer tissues (n = 64) and normal tissues (n = 26) (P = 0.0003). Importantly, the overall survival time of HCC patients who exhibited higher levels of NNT‐AS1 expression was significantly shorter than that of HCC patients who had lower levels of NNT‐AS1 expression (P = 0.0402). Further mechanistic investigation indicated that NNT‐AS1 inhibition significantly decreased the levels of TGF‐β, TGFBR1, and SMAD5 in HCC cells. In HCC tissues, IHC detection showed that relatively high NNT‐AS1 levels were associated with a reduction in infiltrated CD4 lymphocyte numbers. In conclusion, this research identifies a novel mechanism by which NNT‐AS1 impairs CD4 T cell infiltration via activation of the TGF‐β signaling pathway in HCC.

Background: Understanding the spatial heterogeneity of the tumor microenvironment (TME) in pancreatic cancer (PC) remains challenging. Methods: In this study, we performed spatial transcriptomics (ST) to investigate the gene expression features across one normal pancreatic tissue, PC tissue, adjacent tumor tissue, and tumor stroma. We divided 18,075 spatial spots into 22 clusters with t-distributed stochastic neighbor embedding based on gene expression profiles. The biological functions and signaling pathways involved in each cluster were analyzed with gene set enrichment analysis. Results: The results revealed that KRT13+FABP5+ malignant cell subpopulation had keratinization characteristics in the tumor tissue. Fibroblasts from adjacent tumor tissue exhibited a tumor-inhibiting role such as “B-cell activation” and “positive regulation of leukocyte activation.” The FGG+CRP+ inflammatory cancer-associated fibroblasts replaced the islets in tumor stroma. During PC progression, the damage to pancreatic structure and function was heavier in the pancreatic exocrine (AMYA2+PRSS1+) than in the endocrine (INS+GCG+). Conclusion: Our results revealed the spatial heterogeneity of dynamic changes and highlighted the significance of impaired exocrine function in PC.

Micro(mi)RNAs play an essential role in the epithelial-mesenchymal transition (EMT) process in human cancers. This study aimed to uncover the regulatory mechanism of miR-1301-3p on EMT in pancreatic cancer (PC). The miRNA profilings from Gene Expression Omnibus data sets (GSE31568, GSE41372, and GSE32688) demonstrated the downregulation of miR-1301-3p in PC tissues, which was validated with 72 paired PC tissue samples through qRT-PCR detection. The low level of miR-1301-3p was associated with a poor prognosis for PC patients from the PC cohort of The Cancer Genome Atlas and the validation cohort. Gene Ontology analyses indicated that the target genes of miR-1301-3p were involved in cell cycle and adherent junction regulation. In vitro assays revealed that miR-1301-3p suppressed the proliferation and migration abilities of PC cells. Western blotting and luciferase reporter assays suggested that miR-1301-3p inhibited RhoA expression by targeting its 3-untranslated region; RhoA upregulated N-cadherin and vimentin levels; however, it downregulated the E-cadherin level. In conclusion, our study showed that miR-1301-3p could serve as a prognostic biomarker for PC and suppress PC cell malignancy by targeting the RhoA-induced EMT process.

Background: A non‐penetrating vessel closure system (VCS‐AnastoClip^®) may facilitate vascular anastomosis. The purpose of this study is to explore the utilization of a non‐penetratingVCSin orthotopic liver transplantation (OLT).Methods: From January 2015 to February 2017, patients who underwentOLTwere divided into two groups, ie, those who underwent non‐penetratingVCSapplication for inferior vena cava (IVC) and portal vein (PV) reconstructions and those who underwent hand sewing for these purposes. Clinical data, venous anastomotic times, anhepatic phases, and the recovery of liver function were compared between the groups.Results: One hundred and fifteen patients underwentOLT(63 in theVCSgroup and 52 in the suture group). No differences between the two groups were observed in the baseline characteristics. The venous anastomotic time and anhepatic phase in theVCSgroup were significantly shorter than those in the suture group (P < .01). The alanine transaminase and total bilirubin levels in theVCSgroup were comparable to those in the suture group (P = .39 andP = .06, respectively). The complication, mortality, and patency rates of thePVreconstructions did not differ significantly between the two groups.Conclusions: InOLT, the reconstruction of thePVandIVCwith a non‐penetratingVCSsystem is a safe alternative method that has the advantage of shortening the anastomotic time and the anhepatic phase compared to the results of conventional hand suturing. However, the use of thisVCSsystem had no influence on the recovery of graft function.

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