scholarly journals Bioinformatics Analysis of Potential Key Genes in Trastuzumab-Resistant Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Guangda Yang ◽  
Liumeng Jian ◽  
Xiangan Lin ◽  
Aiyu Zhu ◽  
Guohua Wen

Background. This study was performed to identify genes related to acquired trastuzumab resistance in gastric cancer (GC) and to analyze their prognostic value. Methods. The gene expression profile GSE77346 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained by using GEO2R. Functional and pathway enrichment was analyzed by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Search Tool for the Retrieval of Interacting Genes (STRING), Cytoscape, and MCODE were then used to construct the protein-protein interaction (PPI) network and identify hub genes. Finally, the relationship between hub genes and overall survival (OS) was analyzed by using the online Kaplan-Meier plotter tool. Results. A total of 327 DEGs were screened and were mainly enriched in terms related to pathways in cancer, signaling pathways regulating stem cell pluripotency, HTLV-I infection, and ECM-receptor interactions. A PPI network was constructed, and 18 hub genes (including one upregulated gene and seventeen downregulated genes) were identified based on the degrees and MCODE scores of the PPI network. Finally, the expression of four hub genes (ERBB2, VIM, EGR1, and PSMB8) was found to be related to the prognosis of HER2-positive (HER2+) gastric cancer. However, the prognostic value of the other hub genes was controversial; interestingly, most of these genes were interferon- (IFN-) stimulated genes (ISGs). Conclusions. Overall, we propose that the four hub genes may be potential targets in trastuzumab-resistant gastric cancer and that ISGs may play a key role in promoting trastuzumab resistance in GC.

2020 ◽  
Author(s):  
Meng-jie Shan ◽  
Ling-bing Meng ◽  
Peng Guo ◽  
Ya-bin Liu

Abstract Background: Gastric cancer (GC) is the fifth most common cancer in the world and the second leading cause of cancer death. Gastric cancer screening is one of the effective strategies to reduce the mortality. If we use gastric cancer biomarkers with good clinical effect instead of gastroscopy screening, it can achieve early detection, early diagnosis, early treatment. Methods: We download four gene expression profiling datasets of gastric cancer (GSE118916, GSE54129, GSE103236, GSE112369), which obtained from the Gene Expression Omnibus (GEO) database. The DEGs between gastric cancer and adjacent normal tissues were detect to explore genes that may play a key role in gastric cancer. GO and KEGG analyses of overlap genes were performed by the Metascape online database, the protein-protein interaction (PPI) network was analyzed by the STRING online database, and we obtained the hub genes of PPI network via using the Cytoscape software. The survival curve analysis was performed by km-plotter and the stage plots of hub genes was performed by the GEPIA online database. We selected CDH3, LEF1 and MMP7 as candidate biomarkers to construct a back propagation neural network model. Results: This study shows that MMP7, CDH3 and LEF1 are highly expressed in gastric cancer tissues. Conclusions: The joint prediction of the MMP7, CDH3 and LEF1 is helpful for the early diagnosis of cancer.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yaowei Li ◽  
Li Li

Abstract Background Ovarian carcinoma (OC) is a common cause of death among women with gynecological cancer. MicroRNAs (miRNAs) are believed to have vital roles in tumorigenesis of OC. Although miRNAs are broadly recognized in OC, the role of has-miR-182-5p (miR-182) in OC is still not fully elucidated. Methods We evaluated the significance of miR-182 expression in OC by using analysis of a public dataset from the Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we downloaded three mRNA datasets of OC and normal ovarian tissues (NOTs), GSE14407, GSE18520 and GSE36668, from GEO to identify differentially expressed genes (DEGs). Then the targeted genes of hsa-miR-182-5p (TG_miRNA-182-5p) were predicted using miRWALK3.0. Subsequently, we analyzed the gene overlaps integrated between DEGs in OC and predicted target genes of miR-182 by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network and the prognostic effects of the hub genes were analyzed. Results A common pattern of up-regulation for miR-182 in OC was found in our review of the literature. A total of 268 DEGs, both OC-related and miR-182-related, were identified, of which 133 genes were discovered from the PPI network. A number of DEGs were enriched in extracellular matrix organization, pathways in cancer, focal adhesion, and ECM-receptor interaction. Two hub genes, MCM3 and GINS2, were significantly associated with worse overall survival of patients with OC. Furthermore, we identified covert miR-182-related genes that might participate in OC by network analysis, such as DCN, AKT3, and TIMP2. The expressions of these genes were all down-regulated and negatively correlated with miR-182 in OC. Conclusions Our study suggests that miR-182 is essential for the biological progression of OC.


2021 ◽  
Vol 8 ◽  
Author(s):  
Hanxi Wan ◽  
Xinwei Huang ◽  
Peilin Cong ◽  
Mengfan He ◽  
Aiwen Chen ◽  
...  

Idiopathic pulmonary fibrosis (IPF) is a progressive disease whose etiology remains unknown. The purpose of this study was to explore hub genes and pathways related to IPF development and prognosis. Multiple gene expression datasets were downloaded from the Gene Expression Omnibus database. Weighted correlation network analysis (WGCNA) was performed and differentially expressed genes (DEGs) identified to investigate Hub modules and genes correlated with IPF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analysis were performed on selected key genes. In the PPI network and cytoHubba plugin, 11 hub genes were identified, including ASPN, CDH2, COL1A1, COL1A2, COL3A1, COL14A1, CTSK, MMP1, MMP7, POSTN, and SPP1. Correlation between hub genes was displayed and validated. Expression levels of hub genes were verified using quantitative real-time PCR (qRT-PCR). Dysregulated expression of these genes and their crosstalk might impact the development of IPF through modulating IPF-related biological processes and signaling pathways. Among these genes, expression levels of COL1A1, COL3A1, CTSK, MMP1, MMP7, POSTN, and SPP1 were positively correlated with IPF prognosis. The present study provides further insights into individualized treatment and prognosis for IPF.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shuaiqun Wang ◽  
Xiaoling Xu ◽  
Wei Kong

Lung adenocarcinoma (LUAD) is one of the malignant lung tumors. However, its pathology has not been fully understood. The purpose of this study is to identify the hub genes associated with LUAD by bioinformatics methods. Three gene expression datasets including GSE116959, GSE74706, and GSE85841 downloaded from the Gene Expression Omnibus (GEO) database were used in this study. The differentially expressed genes (DEGs) related to LUAD were screened by using the limma package. Gene Ontology (GO) and KEGG analysis of DEGs were carried out through the DAVID website. The protein-protein interaction (PPI) of differentially expressed genes was drawn by the STRING website, and the results were imported into Cytoscape for visualization. Then, the PPI network was analyzed by using MCODE, and the modules with a score greater than 5 were found by using cytoHubba. Finally, the GEPIA database and UALCAN database were used to verify and analyze the survival of hub genes. We identified 67 upregulated genes and 277 downregulated genes from three LUAD datasets. The results of GO analysis showed that the downregulated genes were significantly enriched in matrix adhesion and angiogenesis and upregulated differential genes were significantly enriched in cell adhesion and vascular development. KEGG pathway analysis showed that the differential genes of LUAD were significantly enriched in viral carcinogenesis and adhesion spots. The PPI network of differentially expressed genes consists of 269 nodes and 625 interactions. In addition, three modules with scores greater than 5 and seven hub genes, namely, MCM4, BIRC5, CDC20, CDC25C, FOXM1, GTSE1, and RFC4, playing an important role in the PPI network were screened out. In this study, we obtained the hub genes and pathways related to LUAD, revealing the molecular mechanism and pathogenesis of LUAD, which is helpful for the early detection of LUAD and provides a new idea for the treatment of LUAD.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Weishuang Xue ◽  
Jinwei Li ◽  
Kailei Fu ◽  
Weiyu Teng

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects the quality of life of elderly individuals, while the pathogenesis of AD is still unclear. Based on the bioinformatics analysis of differentially expressed genes (DEGs) in peripheral blood samples, we investigated genes related to mild cognitive impairment (MCI), AD, and late-stage AD that might be used for predicting the conversions. Methods. We obtained the DEGs in MCI, AD, and advanced AD patients from the Gene Expression Omnibus (GEO) database. A Venn diagram was used to identify the intersecting genes. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) were used to analyze the functions and pathways of the intersecting genes. Protein-protein interaction (PPI) networks were constructed to visualize the network of the proteins coded by the related genes. Hub genes were selected based on the PPI network. Results. Bioinformatics analysis indicated that there were 61 DEGs in both the MCI and AD groups and 27 the same DEGs among the three groups. Using GO and KEGG analyses, we found that these genes were related to the function of mitochondria and ribosome. Hub genes were determined by bioinformatics software based on the PPI network. Conclusions. Mitochondrial and ribosomal dysfunction in peripheral blood may be early signs in AD patients and related to the disease progression. The identified hub genes may provide the possibility for predicting AD progression or be the possible targets for treatments.


2022 ◽  
Vol 12 (3) ◽  
pp. 523-532
Author(s):  
Xin Yan ◽  
Chunfeng Liang ◽  
Xinghuan Liang ◽  
Li Li ◽  
Zhenxing Huang ◽  
...  

<sec> <title>Objective:</title> This study aimed to identify the potential key genes associated with the progression and prognosis of adrenocortical carcinoma (ACC). </sec> <sec> <title>Methods:</title> Differentially expressed genes (DEGs) in ACC cells and normal adrenocortical cells were assessed by microarray from the Gene Expression Omnibus database. The biological functions of the classified DEGs were examined by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses and a protein–protein interaction (PPI) network was mapped using Cytoscape software. MCODE software was also used for the module analysis and then 4 algorithms of cytohubba software were used to screen hub genes. The overall survival (OS) examination of the hub genes was then performed by the ualcan online tool. </sec> <sec> <title>Results:</title> Two GSEs (GSE12368, GSE33371) were downloaded from GEO including 18 and 43 cases, respectively. One hundred and sixty-nine DEGs were identified, including 57 upregulated genes and 112 downregulated genes. The Gene Ontology (GO) analyses showed that the upregulated genes were significantly enriched in the mitotic cytokines is, nucleus and ATP binding, while the downregulated genes were involved in the positive regulation of cardiac muscle contraction, extracellular space, and heparin-binding (P < 0.05). The Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway examination showed significant pathways including the cell cycle and the complement and coagulation cascades. The protein– protein interaction (PPI) network consisted of 162 nodes and 847 edges, including mitotic nuclear division, cytoplasmic, protein kinase binding, and cell cycle. All 4 identified hub genes (FOXM1, UBE2C, KIF11, and NDC80) were associated with the prognosis of adrenocortical carcinoma (ACC) by survival analysis. </sec> <sec> <title>Conclusions:</title> The present study offered insights into the molecular mechanism of adrenocortical carcinoma (ACC) that may be beneficial in further analyses. </sec>


2021 ◽  
Author(s):  
Chao Zhang ◽  
Feng Xu ◽  
Fang Fang

Abstract Background: Sepsis-associated acute lung injury (ALI) is a potentially lethal complication associated with a poor prognosis and high mortality worldwide, especially in the outbreak of COVID-19. However, the fundamental mechanisms of this complication were still not fully elucidated. Thus, we conducted this study to identify hub genes and biological pathways of sepsis-associated ALI, mainly focus on two pathways of LPS and HMGB1. Methods: Gene expression profile GSE3037 were downloaded from Gene Expression Omnibus (GEO) database, including 8 patients with sepsis-induced acute lung injury, with 8 unstimulated blood neutrophils, 8 LPS- induced neutrophils and 8 HMGB1-induced neutrophils. Differentially expressed genes (DEGs) identifications, Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, Gene Set Enrichment Analysis (GSEA) and protein-protein interaction (PPI) network constructions were performed to obtain hub genes and relevant biological pathways.Results: We identified 534 and 317 DEGs for LPS- and HMGB1-induced ALI, respectively. The biological pathways involved in LPS- and HMGB1-induced ALI were also identified accordingly. By PPI network analysis, we found that ten hub genes for LPS-induced ALI (CXCL8, TNF, IL6, IL1B, ICAM1, CXCL1, CXCL2, IL1A, IL1RN and CXCL3) and another ten hub genes for HMGB1-induced ALI (CCL20, CXCL2, CXCL1, CCL4, CXCL3, CXCL9, CCL21, CXCR6, KNG1 and SST). Furthermore, by combining analysis, the results revealed that genes of TNF, CCL20, IL1B, NFKBIA, CCL4, PTGS2, TNFAIP3, CXCL2, CXCL1 and CXCL3 were potential biomarkers for sepsis-associated ALI. Conclusions: Our study revealed that ten hub genes associated with sepsis-induced ALI were TNF, CCL20, IL1B, NFKBIA, CCL4, PTGS2, TNFAIP3, CXCL2, CXCL1 and CXCL3, which may serve as genetic biomarkers and be further verified in prospective experimental trials.


2021 ◽  
Vol 11 ◽  
Author(s):  
Meng-jie Shan ◽  
Ling-bing Meng ◽  
Peng Guo ◽  
Yuan-meng Zhang ◽  
Dexian Kong ◽  
...  

BackgroundGastric cancer (GC) is one of the most common cancers all over the world, causing high mortality. Gastric cancer screening is one of the effective strategies used to reduce mortality. We expect that good biomarkers can be discovered to diagnose and treat gastric cancer as early as possible.MethodsWe download four gene expression profiling datasets of gastric cancer (GSE118916, GSE54129, GSE103236, GSE112369), which were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between gastric cancer and adjacent normal tissues were detected to explore biomarkers that may play an important role in gastric cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of overlap genes were conducted by the Metascape online database; the protein-protein interaction (PPI) network was constructed by the STRING online database, and we screened the hub genes of the PPI network using the Cytoscape software. The survival curve analysis was conducted by km-plotter and the stage plots of hub genes were created by the GEPIA online database. PCR, WB, and immunohistochemistry were used to verify the expression of hub genes. A neural network model was established to quantify the predictors of gastric cancer.ResultsThe relative expression level of cadherin-3 (CDH3), lymphoid enhancer-binding factor 1 (LEF1), and matrix metallopeptidase 7 (MMP7) were significantly higher in gastric samples, compared with the normal groups (p&lt;0.05). Receiver operator characteristic (ROC) curves were constructed to determine the effect of the three genes’ expression on gastric cancer, and the AUC was used to determine the degree of confidence: CDH3 (AUC = 0.800, P&lt;0.05, 95% CI =0.857-0.895), LEF1 (AUC=0.620, P&lt;0.05, 95%CI=0.632-0.714), and MMP7 (AUC=0.914, P&lt;0.05, 95%CI=0.714-0.947). The high-risk warning indicator of gastric cancer contained 8&lt;CDH3&lt;15 and 10&lt;expression of LEF1&lt;16.ConclusionsCDH3, LEF1, and MMP7 can be used as candidate biomarkers to construct a neural network model from hub genes, which may be helpful for the early diagnosis of gastric cancer.


2021 ◽  
Author(s):  
Tian-Ao Xie ◽  
Hou-He Li ◽  
Zu-En Lin ◽  
Xiao-Ye Lin ◽  
Xin Meng ◽  
...  

Abstract Background: The Corona Virus Disease 2019 (COVID-19) pandemic poses a serious public health threat to the survival and health of people all over the world. We analyzed related mRNA data and gene expression profiles of human cell lines infected with SARS-CoV-2 obtained from GEO (GSE148729), using bioinformatics tools. Differentially expressed genes (DEGs) of human cells infected with SARS-CoV-2 were identified.Method: The GSE148729 datasets were downloaded from the Gene Expression Omnibus (GEO) database. To explore the Biological significance of DEGs, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the DEGs was performed. Protein-protein interaction (PPI) networks of the DEGs were constructed by using the STRING database. The hub genes were selected using the Cytoscape Software, and a t-test was performed to validate the hub genes.Result: A total of 1241 DEGs were screened, including 1049 up-regulated genes and 192 down-regulated genes. Besides, 10 hub genes were obtained from the PPI network, among which the expression level of CXCL2, Etv7, and HIST1H2BG was found to be statistically significant.Conclusion: In conclusion, bioinformatics analysis reveals genes and cellular pathways that are significantly altered in SARS-CoV-2 infected cells. This is conducive to further guide the clinical study of SARS-CoV-2 and provides new perspectives for vaccine development.


2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Yiting Tian ◽  
Yang Xing ◽  
Zheng Zhang ◽  
Rui Peng ◽  
Luyu Zhang ◽  
...  

Gastric cancer (GC) is one of the most common malignancies in the world, with morbidity and mortality ranking second among all cancers. Accumulating evidences indicate that circular RNAs (circRNAs) are closely correlated with tumorigenesis. However, the mechanisms of circRNAs still remain unclear. This study is aimed at determining hub genes and circRNAs and analyzing their potential biological functions in GC. Expression profiles of mRNAs and circRNAs were downloaded from the Gene Expression Omnibus (GEO) data sets of GC and paracancer tissues. Differentially expressed genes (DEGs) and differentially expressed circRNAs (DE-circRNAs) were identified. The target miRNAs of DE-circRNAs and the bidirectional interaction between target miRNAs and DEGs were predicted. Functional analysis was performed, and the protein-protein interaction (PPI) network and the circRNA-miRNA-mRNA network were established. A total of 456 DEGs and 2 DE-circRNAs were identified with 3 mRNA expression profiles and 2 circRNA expression profiles. GO analysis indicated that DEGs were mainly enriched in extracellular matrix and cell adhesion, and KEGG confirmed that DEGs were mainly associated with focal adhesion, the PI3K-Akt signaling pathway, extracellular matrix- (ECM)- receptor interaction, and gastric acid secretion. 15 hub DEGs (BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, UBE2C, CCNB1, CD44, CXCL8, COL3A1, COL5A2, and THBS1) were identified from the PPI network. Furthermore, the survival analysis indicate that GC patients with a high expression of the following 9 hub DEGs, namely, BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, and UBE2C, had significantly worse overall survival. The circRNA-miRNA-mRNA network was constructed based on 1 circRNA, 15 miRNAs, and 45 DEGs. In addition, the 45 DEGs included 5 hub DEGs. These results suggested that hub DEGs and circRNAs could be implicated in the pathogenesis and development of GC. Our findings provide novel evidence on the circRNA-miRNA-mRNA network and lay the foundation for future research of circRNAs in GC.


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