Analysis of the autophagy gene expression profile of pancreatic cancer based on autophagy-related protein microtubule-associated protein 1A/1B-light chain 3

BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.

Perirenal space blocking restores gastrointestinal function in patients with severe acute pancreatitis

AIM:To investigate effects of perirenal space blocking(PSB)on gastrointestinal function in patients with severe acute pancreatitis(SAP).METHODS:Forty patients with SAP were randomly allocated to receive PSB or no PSB(NPSB).All the SAP patients received specialized medical therapy(SMT).Patients in the PSB group received PSB+SMT when hospitalized and after diagnosis,whereas patients in the NPSB group only received SMT.A modifed gastrointestinal failure(GIF)scoring system was used to assess the gastrointestinal function in SAP patients after admission.Pain severity(visual analog scale,0 to100)was monitored every 24 h for 72 h.RESULTS:Modified GIF score decreased in both groups during the 10-d study period.The median score decrease was initially significantly greater in the PSB group than in the NPSB group after PSB was per-formed.During the 72-h study period,pain intensity decreased in both groups.The median pain decrease was significantly greater in the PSB group than in the NPSB group at single time points.Patients in the PSB group had significantly lower incidences of hospital mortality,multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection,and stayed in the intensive care unit for a shorter duration.However,no difference in terms of operation incidence was found between the two groups.CONCLUSION:PSB could ameliorate gastrointestinal dysfunction or failure during the early stage of SAP.Moreover,PSB administration could improve prognosis and decrease the mortality of SAP patients.

Reduced expression of circulating microRNA-218 in gastric cancer and correlation with tumor invasion and prognosis

AIM:To investigate the expression of microRNA-218(miR-218)in serum from gastric cancer patients and its relationship with clinicopathological characteristics.METHODS:A total of 68 patients with pathologically diagnosed gastric cancer and 56 healthy individuals were recruited to this study.The expression of miR-218was detected in the serum of gastric cancer patients and healthy individuals by quantitative real-time polymerase chain reaction.The clinical data were collectedand analyzed by statistical software.RESULTS:miR-218 was reduced significantly in the serum of gastric cancer patients compared to healthy individuals(1.15±0.08 vs 0.37±0.023;P=0.026).In the gastric cancer group,serum expression of miR-218was lower in patients with metastasis and poorly differentiated cancer compared with non-metastatic and well-differentiated cancer(0.19±0.011 vs 0.45±0.021,P=0.031 and 0.21±0.019 vs 0.49±0.021,P=0.025).Serum miR-218 was found to be significantly associated with gastric cancer metastasis(P=0.003),tumor T stage(P=0.018)and tumor grade(P=0.012).Low serum expression of miR-218 was related to an increase in the stage of gastric cancer.The expression level of miR-218 in the serum was correlated with the3-year survival.Ninety-seven percent of patients with a high level of miR-218 expression survived for 3 years,while only 54%of those with low miR-218 expression survived.CONCLUSION:miR-218 is deregulated in gastric cancer patients and is strongly correlated with tumor stage,grade and metastasis.Serum expression of miR-218 may be a prognostic marker.

Alkynyl-anchored silver nanoclusters in lanthanide metal-organic framework for luminescent thermometer and CO_(2) cycloaddition

In this study,an alkynyl-modified aromatic dicarboxylic acid bifunctional ligand was selected to construct lanthanide compound{[Eu_(4)(ebdc)_(6)(4,4-bpy)_(0.5)(H_(2)O)_(4.5)]·(C_(2)H_(5)OH)_(1.25)(H_(2)O)}_(n)(Eu-MOF,H_(2)ebdc=5-ethynyl-isophthalic acid,4,4-bpy=4,4-bipyridine,MOF=metal-organic framework),of which the uncoordinated alkynyl group would be used to anchor silver nanoclusters(Ag NCs).The Eu-MOF exhibits double emission peaks,located at 492 and 611 nm,respectively,in which the high-energy blue emission is associated with alkynyl-modified ligand while the low-energy red emission belongs to characteristic emission of Eu3+,indicating that ligands can effectively sensitize Eu3+luminescence.The intensity ratio of the dual emission fluorescence peaks of Eu-MOF displays a good linear relationship with temperature,which realizes the detection function in the low temperature region of 75–275 K,the thermal sensitivity reaches 1.5398%·K^(−1).After anchoring the Ag NCs,the high-energy blue emission is significantly quenched,indicating that the Ag NCs are indeed confined into the framework and interact with the alkynyl group,and thus change the overall electronic distribution.This is the first case of anchoring Ag NCs by a luminescent Eu-MOF and studying nanocluster loading by using spectroscopic properties.In addition,the Ag NCs@Eu-MOF also shows a good catalytic activity for cycloaddition reaction from CO_(2)and epoxides.This study not only provides ideas for exploring the changes in optical properties of luminescent MOFs and Ag NCs caused by confinement effect,but also expands their potential applications in various fields.