ObjectiveTo analyze the expression of cold-induced RNA-binding protein (CIRBP) in lung adenocarcinoma and its clinical significance based on bioinformatics, in order to provide a new direction for the study of therapeutic targets for lung adenocarcinoma.MethodsThe CIRBP gene expression data and patient clinical information data in lung adenocarcinoma tissues and adjacent tissues were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The expression of CIRBP in lung adenocarcinoma was analyzed. Furthermore, its relationship with clinicopathological features and prognosis in patients with lung adenocarcinoma was analyzed. GO and KEGG enrichment analysis were carried out for the screened genes. The CIRBP protein interaction network was constructed by STRING, and the correlation analysis was carried out using the GEPIA online website.ResultsThe expression level of CIRBP gene in lung adenocarcinoma tissues was significantly lower than that in adjacent tissues (P<0.01), and its expression level was correlated with T stage and N stage in clinicopathological features. The prognosis of patients with high CIRBP expression in lung adenocarcinoma was significantly better than that with low CIRBP expression. Univariate and multivariate Cox regression analysis showed that CIRBP was an independent prognostic factor in patients with lung adenocarcinoma. GO functional annotation showed its enrichment in organelle fission, nuclear fission, chromosome separation, and DNA replication, etc. KEGG analysis showed that it was mainly involved in cell cycle and DNA replication. Protein interaction network and GEPIA online analysis showed that the expression level of CIRBP was negatively correlated with the expression level of cyclin B2.ConclusionCIRBP gene is down-regulated in lung adenocarcinoma tissues, and its expression level is closely related to patient prognosis. CIRBP gene may be a potential therapeutic target and prognostic marker for lung adenocarcinoma.
Objective To investigate the relationship between miR-3187-5p in peripheral blood and pericardial drainage after coronary artery bypass grafting (CABG) and postoperative atrial fibrillation (POAF). Methods Patients who underwent CABG in the Heart Center of Beijing Chao-Yang Hospital from March to May 2022 were enrolled. Peripheral blood and pericardial drainage were collected at 0 h after surgery (immediate time for patients to return to ICU from operating room) to detect miR-3187-5p, and perioperative confounding factors were also collected. The miR-3187-5p was measured by quantitative real-time PCR and its regulated target genes were analyzed by bioinformatics. Results A total of 15 patients were enrolled, including 9 males and 6 females with an average age of 65.6±8.2 years. The incidence rate of POAF was 40.0%. miR-3187-5p in pericardial drainage at 0 h after surgery was an independent predictor for POAF. A total of 1 642 target genes of miR-3187-5p were predicted. GO function enrichment analysis and KEGG signal pathway enrichment analysis showed that target genes of miR-3187-5p were enriched in TGF-β, MAPK, Wnt and other classical collagen metabolic signal pathways, which might activate collagen metabolism by negatively regulating SMAD6 and other inhibitors of the pathways. Conclusion This study is the first to find that miR-3187-5p in pericardial drainage at 0 h after surgery is a potential, novel, and predictive factor for POAF, which may be related to the regulation of myocardial fibrosis signal pathways like TGF-β, MAPK and Wnt pathways, promoting the early collagen metabolism imbalance after CABG, increasing the collagen deposition in the atrium, and then promoting the early structural reconstruction after CABG and leading to the occurrence of POAF. The result provides a research basis for the accurate prediction and prevention of clinical POAF.
Objective To analyze the relationship between the expression of carbonic anhydrase 3 (CA3) in breast cancer tissues, its prognostic potential and the number of immune cells by a variety of online databases. Methods GEPIA2.0 and TIMER databases were used to analyze the difference of CA3 mRNA expression in breast cancer tissues. Bc-GenExMinerv4.7 database was used to analyze the difference of CA3 mRNA expression in breast cancer subcategories. Kaplan-Meier plotter, Bc-GenExMinerv4.7 and PrognoScan databases were used to analyze the effect of CA3 mRNA expression levels on prognosis of patient. LinkedOmics database was used to analyze of the biological behavior involved in CA3 co-expressed genes. TIMER database was used to analyze the relationship between CA3 mRNA expression and immune cells infiltration in breast cancer tissues. Results The expression of CA3 mRNA in breast cancer tissues was lower than that in normal breast tissues (P<0.05), and the expression levels of CA3 mRNA were higher in ER negative (P<0.05), PR negative (P<0.05), HER2 negative (P<0.05) and no lymphatic metastasis (P<0.05). In addition, the expression level of CA3 in breast cancer patients with high Ki67 expression was lower (P<0.05) and closely related to SBR and NPI grade (P<0.05). Breast cancer patients with low expression of CA3 mRNA had lower overall survivall, recurrence free survival, and disease free survival ( P<0.05). Ten of the top 50 positively correlated co-expressed genes screened out had low risk ratio (P<0.05), and 11 of the top 50 negatively correlated co-expressed genes screened out had high risk ratio (P<0.05). The expression of CA3 mRNA was positively correlated with CD4+ T cells and CD8+ T cells in breast cancer tissues (rs=0.175, P<0.001; rs=0.137, P<0.001), and negatively correlated with T cell failure markers LAG3, TIM-3 and PVRL2 (rs=–0.100, P<0.01; rs=–0.143, P<0.001; rs=–0.082, P<0.05). Conclusions The low expression of CA3 mRNA in breast cancer tissues is correlated with the occurrence, development and prognosis of breast cancer. CA3 can be used as a potential independent prognostic marker for breast cancer and may be related to immune infiltration.
ObjectiveTo explore the significance of mesenchymal epithelial transition factor (MET) as a clinical prognostic evaluation index for patients with pancreatic cancer based on bioinformatics analysis.MethodsThe GSE28735 and GSE62452 gene chips from GEO database were downloaded and the difference of MET gene expression between cancer and adjacent cancerous tissues were analyzed by bioinformatics. We downloaded pancreatic cancer gene chip from TCGA database to analyze the correlation between MET gene expression and clinicopathological features of pancreatic cancer patients and prognosis risk. Finally, the possible molecular mechanism of MET involved in pancreatic carcinogenesis was analyzed by GO and KEGG enrichment analysis.ResultsThe expression level of MET gene in pancreatic cancer tissues was significantly higher than that in adjacent cancerous tissues (P<0.001). The overall survival and disease-free survival of pancreatic cancer patients in the high MET gene expression group were lower than those in the low expression group (P<0.001). The expression level of MET gene was related to the age of pancreatic cancer patients, T stage, and histological grading of tumors (P<0.05), and high MET gene expression, age >65 years, and N1 stage were independent risk factors affecting the prognosis of pancreatic cancer patients. KEGG enrichment analysis showed that MET was mainly related to PI3K/AKT signaling pathway, FAK signaling pathway, and cancer transcription dysregulation and so on.ConclusionMET may be a valuable tumor marker for pancreatic cancer and can predict the poor prognosis of patients with pancreatic cancer.
ObjectiveTo explore the mechanism of paucigranulocytic asthma and to find therapeutic target for paucigranulocytic asthma.MethodsGSE143303 data and platform information were downloaded from GEO. Gene Set Enrichment Analysis were performed to construct positive and negative gene-gene interaction network correlation with paucigranulocytic asthma. Differential expression analysis, pathway commonality analysis were performed with R language.ResultsGSE143303 data set contained 47 endobronchial biopsies from adult (16 cases of paucigranulocytic asthma, 13 cases of healthy control). Compared with control group, the paucigranulocytic asthma group had 115 differential genes set (37 positive and 78 negative). The results of pathway commonality analysis showed that the crosslink existed within the negative gene-gene interaction network correlation with paucigranulocytic asthma. Among these, most of the genes belonged to the protein HLA gene family. Differential expression analysis show that HLA-DQB1, HLA-DRB5 were differential genes and TNFRSF13B was significantly downregulated genes in the intersect genes.ConclusionTNFRSF13B, HLA-DQB1, HLA-DRB5 and regulatory networks associated with them are the crucial factors contributing to paucigranulocytic asthma.
Objective To identify potential hub genes and key pathways in the early period of septic shock via bioinformatics analysis. MethodsThe gene expression profile GSE110487 dataset was downloaded from the Gene Expression Omnibus database. Differentially expressed genes were identified by using DESeq2 package of R project. Then Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were constructed to investigated pathways and biological processes using clusterProfiler package. Subsequently, protein-protein interaction (PPI) network was mapped using ggnetwork package and the molecular complex detection (MCODE) analysis was implemented to further investigate the interactions of differentially expressed genes using Cytoscape software. Results A total of 468 differentially expressed genes were identified in septic shock patients with different responses who accepted early supportive hemodynamic therapy, including 255 upregulated genes and 213 downregulated genes. The results of GO and the KEGG pathway enrichment analysis indicated that these up-regulated genes were highly associated with the immune-related biological processes, and the down-regulated genes are involved in biological processes related to organonitrogen compound, multicellular organismal process, ion transport. Finally, a total of 23 hub genes were identified based on PPI and the subcluster analysis through MCODE software plugin in Cytoscape, which included 19 upregulated hub genes, such as CD28, CD3D, CD8B, CD8A, CD160, CXCR6, CCR3, CCR8, CCR9, TLR3, EOMES, GZMB, PTGDR2, CXCL8, GZMA, FASLG, GPR18, PRF1, IDO1, and additional 4 downregulated hub genes, such as CNR1, GPER1, TMIGD3, GRM2. KEGG pathway enrichment analysis and GO functional annotation showed that differentially expressed genes were primarily associated with the items related to cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity, hematopoietic cell lineage, T cell receptor signaling pathway, phospholipase D signaling pathway, cell adhesion molecules, viral protein interaction with cytokine and cytokine receptor, primary immunodeficiency, graft-versus-host disease, type 1 diabetes mellitus. Conclusions Some lymphocytes such as T cells and natural killer cells, cytokines and chemokines participate in the immune process, which plays an important role in the early treatment of septic shock, and CD160, CNR1, GPER1, and GRM2 may be considered as new biomarkers.
ObjectiveAlthough evidence links idiopathic pulmonary fibrosis (IPF) and diabetes mellitus (DM), the exact underlying common mechanism of its occurrence is unclear. This study aims to explore further the molecular mechanism between these two diseases. MethodsThe microarray data of idiopathic pulmonary fibrosis and diabetes mellitus in the Gene Expression Omnibus (GEO) database were downloaded. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify co-expression genes related to idiopathic pulmonary fibrosis and diabetes mellitus. Subsequently, differentially expressed genes (DEGs) analysis and three public databases were employed to analyze and screen the gene targets related to idiopathic pulmonary fibrosis and diabetes mellitus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape. In addition, common microRNAs (miRNAs), common in idiopathic pulmonary fibrosis and diabetes mellitus, were obtained from the Human microRNA Disease Database (HMDD), and their target genes were predicted by miRTarbase. Finally, we constructed a common miRNAs-mRNAs network by using the overlapping genes of the target gene and the shared gene. ResultsThe results of common gene analysis suggested that remodeling of the extracellular matrix might be a key factor in the interconnection of DM and IPF. Finally, hub genes (MMP1, IL1R1, SPP1) were further screened. miRNA-gene network suggested that has-let-19a-3p may play a key role in the common molecular mechanism between IPF and DM. ConclusionsThis study provides new insights into the potential pathogenic mechanisms between idiopathic pulmonary fibrosis and diabetes mellitus. These common pathways and hub genes may provide new ideas for further experimental studies.
ObjectiveTo explore the mechanism of DDX46 regulation of esophageal squamous cell carcinoma.MethodsPicture signals of fluorescence in gene array were scanned and differential expression of gene in two groups (a DDX46-shRNA-LV group and a control-LV group) were compared by GCOSvL.4 software. These differential expressed genes were analyzed by bioinformatics methods finally, and validated by quantitative real time polymerase chain reaction (qRT-PCR) analysis.ResultsAccording to the screening criteria of fold change ≥2 and P<0.05, 1 006 genes were differentially expressed after DDX46 knockdown, including 362 up-regulated and 644 down-regulated genes. Bioinformatics analysis and gene co-expression network building identified that these differentially expressed genes were mainly involved in cell cycle, proliferation, apoptosis, adhesion, energy metabolism, immune response, etc. Phosphatidylinositol 3-kinase (PI3K) was the key molecule in the network. The results of RT-qPCR were completely consistent with the results of gene microarra.ConclusionBioinformatics can effectively exploit the microarray data of esophageal squamous cell carcinoma after DDX46 knockdown, which provides a valuable clue for further exploration of DDX46 tumorigenesis mechanism and helps to find potential drug therapy.
Objective A series of bioinformatics methods were used to identify ferroptosis related biomarkers in lupus nephritis (LN). Methods We retrieved sequencing data of GSE112943 from the GEO (Gene Expression Omnibus) database and screened LN differentially expressed genes. We searched for ferroptosis-related gene (FRG) through FerrDb database, and screened LN-FRG. We conducted enrichment analysis on the LN-FRGs using David online bioinformatics database and screened the core LN-FRG using cytoHubba. We used external data sets to verify the core LN-FRGs, constructed competing endogenous RNA networks, and conducted molecular docking analysis. Results A total of 37 LN-FRGs were selected through screening. These genes are mainly enriched in inflammation, immune regulation and ferroptosis related signaling pathways. Through the cytoHubba and external dataset validation, the key core LN-FRG of ATF3 (activating transcription factor 3) was ultimately identified, and its expression was significantly increased in LN (P<0.05). Molecular docking analysis showed that ATF3 was closely bound to SLC7A11 and NRF2, and may participate in the occurrence and development of LN through the microRNA-27-ATF3 regulation axis. Conclusion The pivotal gene ATF3 may participate in the inflammation and immune injury of LN through ferroptosis.
Objective To explore key genes and mechanisms of depression aggravating Crohn disease. Methods In March 2023, the Public Health Genomics and Precision Health Knowledge Base and Gene Expression Omnibus database were used to identify the overlapping differentially expressed genes between Crohn disease and depression and the key genes were screened by Metascape, STRING, Cytoscape, and protein interaction network analysis. The Gene Expression Omnibus database was used to analyze the correlations between key genes and clinical pathologies such as Crohn Disease Endoscopic Index of Severity and intestinal microvilli length. Results There were 137 overlapping differentially expressed genes between Crohn disease and depression, and 25 key genes were further screened out. Among them, CREB1, FKBP5, MAPT, NTSR1, OXTR, PROK2, POMC, HTR2B, and PPARGC1A genes were significantly correlated with multiple clinical parameters. The functions of PROK2 and PROK2-related genes were mainly enriched in neutrophil and granulocyte migration, neutrophil and granulocyte chemotaxis, etc. Conclusions There are 25 key genes, especially CREB1, FKBP5, MAPT, NTSR1, OXTR, PROK2, POMC, HTR2B, and PPARGC1A, that possibly contribute to the establishment and deterioration of Crohn disease caused by depressive disorder. Among these genes, PROK2 showes the possibility of regulating immune cell (neutrophils and CD8+ T cells) infiltration.