scholarly journals Identification of Biomarkers and Study of Mechanisms Related to Metastatic of Osteosarcoma Based on Integrated Bioinformatics Analyses

Author(s):  
Guangzhi Wu ◽  
Minglei Zhang

Abstract BackgroundOsteosarcoma (OS) is a serious threat to public health. Because of high morbidity and fairly complicated pathogenesis. The study aim to identify candidate biomarkers and research the molecular mechanisms correlated of patients with metastatic OS. MethodsThe GSE21257 was downloaded from Gene Expression Omnibus(GEO) database, and the differentially expressed RNAs (DERs) were identified and functional enriched analysis by statistical soft-ware in R. Subsequently, the co-expression modules and its clinical characteristics of OS were identified by weighted gene co-expression network analysis (WGCNA) Following, the KEGG pathways directly related to metastatic OS was to researched by the Comparative Toxicogenomics Database 2019 update (CTD). Finally, the “survival” package in R was used to survival analysis and the DERs were verified using another independent profiling GSE14827. ResultsA total of 1,464 DERs were classified including 702 up-regulated and 762 down-regulated. In addition, a total of 1248 DERs were obtained by WGCNA analysis, the blue modules is the highest negative correlation (P=0) and the turquoise modules is highest positive correlation (P=3E-196) among all correlations with OS metastatic. The lncRNA-mRNA co-expression network including 4 lncRNAs and 507 mRNAs, and the cytokine-cytokine receptor interaction and JAK-STAT signaling pathway were found significantly correlation with metastatic. Finally, the increased expression levels of IFNGR1, lower DLEU1 and DLEU2 related to better prognosis. Which were significantly consistent in the another independent profiling GSE14827. ConclusionsA bioinformatics analysis related to the IFNGR1, DLEU1 and DLEU2 may as candidate biomarkers for metastatic OS.

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Benzhuo Zhang ◽  
Wei Huang ◽  
Mingquan Yi ◽  
Chunxu Xing

Atherosclerotic cerebral infarction (ACI) seriously threatens the health of the senile patients, and the strategies are urgent for the diagnosis and treatment of ACI. This study investigated the mRNA profiling of the patients with ischemic stroke and atherosclerosis via excavating the datasets in the GEO database and attempted to reveal the biomarkers and molecular mechanism of ACI. In this study, GES16561 and GES100927 were obtained from Gene Expression Omnibus (GEO) database, and the related differentially expressed genes (DEGs) were analyzed with R language. Furthermore, the DEGs were analyzed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Besides, the protein-protein interaction (PPI) network of DEGs was analyzed by STRING database and Cytoscape. The results showed that 133 downregulated DEGs and 234 upregulated DEGs were found in GES16561, 25 downregulated DEGs and 104 upregulated DEGs were found in GSE100927, and 6 common genes were found in GES16561 and GES100927. GO enrichment analysis showed that the functional models of the common genes were involved in neutrophil activation, neutrophil degranulation, neutrophil activation, and immune response. KEGG enrichment analysis showed that the DEGs in both GSE100927 and GSE16561 were connected with the pathways including Cell adhesion molecules (CAMs), Cytokine-cytokine receptor interaction, Phagosome, Antigen processing and presentation, and Staphylococcus aureus infection. The PPI network analysis showed that 9 common DEGs were found in GSE100927 and GSE16561, and a cluster with 6 nodes and 12 edges was also identified by PPI network analysis. In conclusion, this study suggested that FCGR3A and MAPK pathways were connected with ACI.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Songbai Yang ◽  
Xiaolong Zhou ◽  
Yue Pei ◽  
Han Wang ◽  
Ke He ◽  
...  

Estrus is an important factor for the fecundity of sows, and it is involved in ovulation and hormone secretion in ovaries. To better understand the molecular mechanisms of porcine estrus, the expression patterns of ovarian mRNA at proestrus and estrus stages were analyzed using RNA sequencing technology. A total of 2,167 differentially expressed genes (DEGs) were identified (P≤0.05, log2  Ratio≥1), of which 784 were upregulated and 1,383 were downregulated in the estrus compared with the proestrus group. Gene Ontology (GO) enrichment indicated that these DEGs were mainly involved in the cellular process, single-organism process, cell and cell part, and binding and metabolic process. In addition, a pathway analysis showed that these DEGs were significantly enriched in 33 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including cell adhesion molecules, ECM-receptor interaction, and cytokine-cytokine receptor interaction. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) confirmed the differential expression of 10 selected DEGs. Many of the novel candidate genes identified in this study will be valuable for understanding the molecular mechanisms of the sow estrous cycle.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Bojun Xu ◽  
Lei Wang ◽  
Huakui Zhan ◽  
Liangbin Zhao ◽  
Yuehan Wang ◽  
...  

Objectives. Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients. Methods. GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN. Results. There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN. Conclusions. We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Suxiang Lu ◽  
Qian Xiong ◽  
Kang Du ◽  
Xiaoni Gan ◽  
Xuzhen Wang ◽  
...  

Abstract Background Polypterus senegalus can fully regenerate its pectoral lobed fins, including a complex endoskeleton, with remarkable precision. However, despite the enormous potential of this species for use in medical research, its regeneration mechanisms remain largely unknown. Methods To identify the differentially expressed proteins (DEPs) during the early stages of lobed fin regeneration in P. senegalus, we performed a differential proteomic analysis using isobaric tag for relative and absolute quantitation (iTRAQ) approach based quantitative proteome from the pectoral lobed fins at 3 time points. Furthermore, we validated the changes in protein expression with multiple-reaction monitoring (MRM) analysis. Results The experiment yielded a total of 3177 proteins and 15,091 unique peptides including 1006 non-redundant (nr) DEPs. Of these, 592 were upregulated while 349 were downregulated after lobed fin amputation when compared to the original tissue. Bioinformatics analyses showed that the DEPs were mainly associated with Ribosome and RNA transport, metabolic, ECM-receptor interaction, Golgi and endoplasmic reticulum, DNA replication, and Regulation of actin cytoskeleton. Conclusions To our knowledge, this is the first proteomic research to investigate alterations in protein levels and affected pathways in bichirs’ lobe-fin/limb regeneration. In addition, our study demonstrated a highly dynamic regulation during lobed fin regeneration in P. senegalus. These results not only provide a comprehensive dataset on differentially expressed proteins during the early stages of lobe-fin/limb regeneration but also advance our understanding of the molecular mechanisms underlying lobe-fin/limb regeneration.


2019 ◽  
Vol 8 ◽  
pp. 1407
Author(s):  
Mohammad Rostami-Nejad ◽  
Reza Vafaee ◽  
Mohammad Javad Ehsani-Ardakani ◽  
Nika Aghamohammadi ◽  
Aliasghar Keramatinia ◽  
...  

Background: Celiac disease (CD) is an immunological intestinal disorder, which is characterized by response to gluten. In addition to the environmental factors and dysbiosis of the gut microbiota, genetic susceptibility has an important role in the pathogenesis of this multifactorial disorder. Therefore, this study aims to present the crucial involved genes in CD pathogenesis. Materials and Methods: In this bioinformatics analysis study, significant differentially expressed genes of intraepithelial lymphocytes (IELs) samples of celiac patients versus normal patients from Gene Expression Omnibus (GEO) database were screened via the protein-protein interaction (PPI) network. The critical nodes based on degree values, betweenness centrality, and fold changes were determined and enriched by ClueGO to find relative biological terms. Results: According to the network analysis, five central nodes including IL2, PIK3CA, PRDM10, AKT1, and SRC and eight significant differentially expressed genes (DEGs) were determined as the critical genes related to CD. Also, CD4+, CD25+, alpha-beta regulatory T cell differentiation are identified as prominent biological terms in the celiac disease patients. Conclusion: There is a possible biomarker panel related to CD that can be used as a therapeutic or diagnostic tool to manage the disease. [GMJ.2019;8:e1407]


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Qianru Li ◽  
Liang Zhang ◽  
Jinfang Jiang ◽  
Yangyang Zhang ◽  
Xiaomeng Wang ◽  
...  

Abstract Background Rhabdomyosarcoma (RMS), a common soft-tissue malignancy in pediatrics, presents high invasiveness and mortality. However, besides known changes in the PAX3/7-FOXO1 fusion gene in alveolar RMS, the molecular mechanisms of the disease remain incompletely understood. The purpose of the study is to recognize potential biomarkers related with RMS and analyse their molecular mechanism, diagnosis and prognostic significance. Methods The Gene Expression Omnibus was used to search the RMS and normal striated muscle data sets. Differentially expressed genes (DEGs) were filtered using R software. The DAVID has become accustomed to performing functional annotations and pathway analysis on DEGs. The protein interaction was constructed and further processed by the STRING tool and Cytoscape software. Kaplan–Meier was used to estimate the effect of hub genes on the ending of sarcoma sufferers, and the expression of these genes in RMS was proved by real-time polymerase chain reaction (RT-PCR). Finally, the expression of CDK1 and CCNB1 in RMS was validated by immunohistochemistry (IHC). Results A total of 1932 DEGs were obtained, amongst which 1505 were up-regulated and 427were down-regulated. Up-regulated genes were largely enriched in the cell cycle, ECM-receptor interaction, PI3K/Akt and p53 pathways, whilst down-regulated genes were primarily enriched in the muscle contraction process. CDK1, CCNB1, CDC20, CCNB2, AURKB, MAD2L1, HIST2H2BE, CENPE, KIF2C and PCNA were identified as hub genes by Cytoscape analyses. Survival analysis showed that, except for HIST2H2BE, the other hub genes were highly expressed and related to poor prognosis in sarcoma. RT-PCR validation showed that CDK1, CCNB1, CDC20, CENPE and HIST2H2BE were significantly differential expression in RMS compared to the normal control. IHC revealed that the expression of CDK1 (28/32, 87.5%) and CCNB1 (26/32, 81.25%) were notably higher in RMS than normal controls (1/9, 11.1%; 0/9, 0%). Moreover, the CCNB1 was associated with the age and location of the patient’s onset. Conclusions These results show that these hub genes, especially CDK1 and CCNB1, may be potential diagnostic biomarkers for RMS and provide a new perspective for the pathogenesis of RMS.


2021 ◽  
Author(s):  
Jian Zhang ◽  
Zehan Liu ◽  
Shuai Ren ◽  
Zilong Shen ◽  
Kecheng Han ◽  
...  

Abstract Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive bone disorder that is characterized by femoral head collapse and hip joint dysfunction. To elucidate the biomarkers of SONFH, the GSE123568 dataset was downloaded from the Gene Expression Omnibus (GEO) database. A total of 436 differentially expressed SONFH genes were screened in comparison with non-SONFH genes. Six biological processes and four KEGG pathways were enriched in SONFH by GSEA, and 68 candidate genes that were involved in these pathways were selected for subsequent analysis. Moreover, through an ingenuity pathway analysis, we obtained 10 canonical pathways and 20 molecule function modules related to SONFH, and acquired 121 candidate genes. Furthermore, we identified ACP5, TNF, and MMP8 as the genes most related to SONFH according to the VarElect and MalaCards database. Based on these hub genes, the targeted miRNAs and the lncRNAs were predicted. Finally, the ceRNA network was constructed by using ACP5, TNF, MMP8, seven miRNAs, and 956 candidate lncRNAs. In conclusion, the ACP5, TNF, and MMP8 might be potential biomarkers of SONFH.


2020 ◽  
Author(s):  
Yiyun Cao ◽  
Taotao Liu ◽  
Zhengqian Li ◽  
Jiao Yang ◽  
Lijun Ma ◽  
...  

Abstract Background An excessive neuroinflammatory response involved in the pathogenesis of postoperative cognitive dysfunction (POCD), which increases morbidity and mortality. However, the precise mechanism remains unclear. Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to be anti-inflammatory. Therefore, we aimed to explore whether TSA can inhibit the surgery-induced neuroinflammation and improve POCD and further reveal the complex neuropathogenesis underlying POCD. Methods To explore the molecular mechanisms by which surgery-induced POCD in aged rats, TSA (1 mg/kg) was intraperitoneally injected, and hippocampal microglial activation and neuroinflammation were observed. We investigated changes in the protein profile of the hippocampus using a proteomics approach [isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano liquid chromatography-mass spectrometry] at the peak of surgery-induced neuroinflammation, and significant alterations of proteins were verified using western blotting and immunofluorescence. Then, proteins associated with signaling pathways in the surgery + TSA and surgery groups were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results After laparotomy, aged rats had prolonged escape latencies on days 4 and 5 postsurgery, spent less time in the target quadrant than control rats (p < 0.05), and exhibited excessive hippocampal microglia activation and IL-1β and TNF-α release. iTRAQ and bioinformatics analyses at 6 h after surgery showed that neurofilaments (NFs), including the NEFH, NEFM and NEFL proteins, were significantly upregulated, and TSA pretreatment could mitigate these changes. Subsequently, KEGG analysis revealed that nine pathways were enriched in the surgery + TSA group vs. the surgery group (p < 0.05). Among them, two signaling pathways, “focal adhesion” and “ECM-receptor interaction”, were associated with significant upregulation of collagen and downregulation of NF proteins, indicating these as possibly important pathways involved in NF degradation in the hippocampus of aged brains after surgery-induced POCD. Conclusion Surgery-induced neuroinflammation upregulated NFs, resulting NF degradation and aggregation in the hippocampus of aged rats, which might lead to hippocampus-independent learning and memory impairment, contributing to POCD. Additionally, TSA diminished surgery-induced neuroinflammatory responses and modulated the NF-associated changes in cognitive dysfunction in aged brains, which might be related to activation of the “focal adhesion” and “ECM-receptor interaction” pathways.


2021 ◽  
Author(s):  
Chao Zhao ◽  
Han Wang ◽  
Conglei Dong ◽  
Huijun Kang ◽  
Fei Wang

Abstract Objective: Through the bioinformatics analysis, to identify the genes and pathways of nonsteroidal anti-inflammatory drugs(NSARDs) acting on synovia from women with knee osteoarthritis (KOA), and to provide reference for clinical application. Methods: We downloaded the gene microarray datasets with the accession number of GSE55457 and GSE55584 from the Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) database, including 5 untreated KOA patients, 9 NSARDs treated KOA patients and 2 patients without KOA The samples in the untreated KOA group and the NSARDs treated KOA group were used for main analysis. The samples in the untreated KOA group and the normal control group were used for cooperative analysis. Then we performed robust multi-array (RMA) normalization with affy R programming package. After that, differential expression genes (DEGs) in main analysis and cooperative analysis were identified based on limma package separately. Screening the common DEGs from main analysis and cooperative analysis. Enriched gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs were obtained through the Database for Annotation, Visualization and Integrated Discovery (DAVID). What's more, protein-protein interaction (PPI) network was constructed, and we identified modules of PPI network through Cytoscape to screen valuable targets. The value of gene expression fold change (FC) ≥1.4 or ≤1/1.4, and P <0.05 were used as the screening conditions. P <0.05 and Associated genes count>5 were used as the screening conditions.Results: There were 338 DEGs in main analysis. Among them, 211 genes were up-regulated and 127 genes were down-regulated. There were 7005 DEGs in cooperative analysis. Among them, 6952 genes were up-regulated and 53 genes were down-regulated. A total of 129 common DEGs were identified between main analysis and cooperative analysis. There are 2 biological processes, 3 cell components and 2 molecular functions for the enrichment of differentially expressed genes.Conclusion: NSARDs may play a certain role in synovia from women with KOA by regulating the mRNA expressions of il-6, TNFRSF11A and CSF1R, which may become one of the indicators for monitoring the efficacy of NSAIDs.


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