scholarly journals Identification of Hub Genes and Pathways Associated With Idiopathic Pulmonary Fibrosis via Bioinformatics Analysis

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.

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 ◽  
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.


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):  
Weijia Lu ◽  
Yunyu Wu ◽  
CanXiong Lu ◽  
Ting Zhu ◽  
ZhongLu Ren ◽  
...  

Abstract Objective MicroRNAs (MiRNAs) is considered to play an important role in the occurrence and development of ovarian cancer(OC). Although miRNAs has been widely recognized in ovarian cancer, the role of hsa-miR-30a-5p (miR-30a) in OC has not been fully elucidated. Methods Through the analysis of public data sets in Gene Expression Omnibus (GEO) database and literature review, the significance of miR-30a expression in OC is evaluated. Three mRNA datasets of OC and normal ovarian tissue, GSE14407, GSE18520 and GSE36668, were downloaded from GEO to find the differentially expressed gene (DEG). Then the target genes of hsa-miR-30a-5p were predicted by miRWALK3.0 and TargetScan. Then, the gene overlap between DEG and the predicted target genes of miR-30a in OC was analyzed by Gene Ontology (GO) enrichment analysis. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape, and the effect of HUB gene on the prognosis of OC was analyzed. Results A common pattern of up-regulation of miR-30a in OC was found. A total of 225 DEG, were identified, both OC-related and miR-30a-related. Many DEG are enriched in the interactions of intracellular matrix tissue, ion binding and biological process regulation. Among the 10 major Hub genes analyzed by PPI, five Hub genes were significantly related to the overall poor survival of OC patients, in which the low expression of ESR1 ,MAPK10, Tp53 and the high expression of YKT ,NSF were related to poor prognosis of OC.


2021 ◽  
Author(s):  
Siwei Su ◽  
Wenjun Jiang ◽  
Xiaoying Wang ◽  
Sen Du ◽  
Lu Zhou ◽  
...  

Abstract ObjectiveThis study aims to explore the key genes and investigated the different signaling pathways of rheumatoid arthritis (RA) between males and females.Data and MethodsThe gene expression data of GSE55457, GSE55584, and GSE12021 were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using R software. Then, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein interaction (PPI) networks of DEGs were constructed by Cytoscape 3.6.0. ResultsA total of 416 upregulated DEGs and 336 downregulated DEGs were identified in males, and 744 upregulated DEGs and 309 downregulated DEGs were identified in females.IL6, MYC, EGFR, FOS and JUN were considered as hub genes in RA pathogenesis in males, while IL6, ALB, PTPRC, CXCL8 and CCR5 were considered as hub genes in RA pathogenesis in females. ConclusionIdentified DEG may be involved in the different mechanisms of RA disease progression between males and females, and they are treated as prognostic markers or therapeutic targets for males and females. The pathogenesis mechanism of RA is sex-dependent.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jingni Wu ◽  
Xiaomeng Xia ◽  
Ye Hu ◽  
Xiaoling Fang ◽  
Sandra Orsulic

Endometriosis has been associated with a high risk of infertility. However, the underlying molecular mechanism of infertility in endometriosis remains poorly understood. In our study, we aimed to discover topologically important genes related to infertility in endometriosis, based on the structure network mining. We used microarray data from the Gene Expression Omnibus (GEO) database to construct a weighted gene co-expression network for fertile and infertile women with endometriosis and to identify gene modules highly correlated with clinical features of infertility in endometriosis. Additionally, the protein–protein interaction network analysis was used to identify the potential 20 hub messenger RNAs (mRNAs) while the network topological analysis was used to identify nine candidate long non-coding RNAs (lncRNAs). Functional annotations of clinically significant modules and lncRNAs revealed that hub genes might be involved in infertility in endometriosis by regulating G protein-coupled receptor signaling (GPCR) activity. Gene Set Enrichment Analysis showed that the phospholipase C-activating GPCR signaling pathway is correlated with infertility in patients with endometriosis. Taken together, our analysis has identified 29 hub genes which might lead to infertility in endometriosis through the regulation of the GPCR network.


2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Yanzhe Wang ◽  
Wenjuan Cai ◽  
Liya Gu ◽  
Xuefeng Ji ◽  
Qiusheng Shen

Purpose. Atrial fibrillation (AF) is the most frequent arrhythmia in clinical practice. The pathogenesis of AF is not yet clear. Therefore, exploring the molecular information of AF displays much importance for AF therapy. Methods. The GSE2240 data were acquired from the Gene Expression Omnibus (GEO) database. The R limma software package was used to screen DEGs. Based on the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) databases, we conducted the functions and pathway enrichment analyses. Then, the STRING and Cytoscape software were employed to build Protein-Protein Interaction (PPI) network and screen for hub genes. Finally, we used the Cell Counting Kit-8 (CCK-8) experiment to explore the effect of hub gene knockdown on the proliferation of AF cells. Result. 906 differentially expressed genes (DEGs), including 542 significantly upregulated genes and 364 significantly downregulated genes, were screened in AF. The genes of AF were mainly enriched in vascular endothelial growth factor-activated receptor activity, alanine, regulation of histone deacetylase activity, and HCM. The PPI network constructed of significantly upregulated DEGs contained 404 nodes and 514 edges. Five hub genes, ASPM, DTL, STAT3, ANLN, and CDCA5, were identified through the PPI network. The PPI network constructed by significantly downregulated genes contained 327 nodes and 301 edges. Four hub genes, CDC42, CREB1, AR, and SP1, were identified through this PPI network. The results of CCK-8 experiments proved that knocking down the expression of CDCA5 gene could inhibit the proliferation of H9C2 cells. Conclusion. Bioinformatics analyses revealed the hub genes and key pathways of AF. These genes and pathways provide information for studying the pathogenesis, treatment, and prognosis of AF and have the potential to become biomarkers in AF treatment.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jiamei Liu ◽  
Shengye Liu ◽  
Xianghong Yang

BackgroundDespite advances in the understanding of neoplasm, patients with cervical cancer still have a poor prognosis. Identifying prognostic markers of cervical cancer may enable early detection of recurrence and more effective treatment.MethodsGene expression profiling data were acquired from the Gene Expression Omnibus database. After data normalization, genes with large variation were screened out. Next, we built co-expression modules by using weighted gene co-expression network analysis to investigate the relationship between the modules and clinical traits related to cervical cancer progression. Functional enrichment analysis was also applied on these co-expressed genes. We integrated the genes into a human protein-protein interaction (PPI) network to expand seed genes and build a co-expression network. For further analysis of the dataset, the Cancer Genome Atlas (TCGA) database was used to identify seed genes and their correlation to cervical cancer prognosis. Verification was further conducted by qPCR and the Human Protein Atlas (HPA) database to measure the expression of hub genes.ResultsUsing WGCNA, we identified 25 co-expression modules from 10,016 genes in 128 human cervical cancer samples. After functional enrichment analysis, the magenta, brown, and darkred modules were selected as the three most correlated modules for cancer progression. Additionally, seed genes in the three modules were combined with a PPI network to identify 31 tumor-specific genes. Hierarchical clustering and Gepia results indicated that the expression quantity of hub genes NDC80, TIPIN, MCM3, MCM6, POLA1, and PRC1 may determine the prognosis of cervical cancer. Finally, TIPIN and POLA1 were further filtered by a LASSO model. In addition, their expression was identified by immunohistochemistry in HPA database as well as a biological experiment.ConclusionOur research provides a co-expression network of gene modules and identifies TIPIN and POLA1 as stable potential prognostic biomarkers for cervical cancer.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0254326
Author(s):  
Yike Zhu ◽  
Dan Huang ◽  
Zhongyan Zhao ◽  
Chuansen Lu

Background Epilepsy is one of the most common brain disorders worldwide. It is usually hard to be identified properly, and a third of patients are drug-resistant. Genes related to the progression and prognosis of epilepsy are particularly needed to be identified. Methods In our study, we downloaded the Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE143272. Differentially expressed genes (DEGs) with a fold change (FC) >1.2 and a P-value <0.05 were identified by GEO2R and grouped in male, female and overlapping DEGs. Functional enrichment analysis and Protein-Protein Interaction (PPI) network analysis were performed. Results In total, 183 DEGs overlapped (77 ups and 106 downs), 302 DEGs (185 ups and 117 downs) in the male dataset, and 750 DEGs (464 ups and 286 downs) in the female dataset were obtained from the GSE143272 dataset. These DEGs were markedly enriched under various Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. 16 following hub genes were identified based on PPI network analysis: ADCY7, C3AR1, DEGS1, CXCL1 in male-specific DEGs, TOLLIP, ORM1, ELANE, QPCT in female-specific DEGs and FCAR, CD3G, CLEC12A, MOSPD2, CD3D, ALDH3B1, GPR97, PLAUR in overlapping DEGs. Conclusion This discovery-driven study may be useful to provide a novel insight into the diagnosis and treatment of epilepsy. However, more experiments are needed in the future to study the functional roles of these genes in epilepsy.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9633
Author(s):  
Jie Meng ◽  
Rui Su ◽  
Yun Liao ◽  
Yanyan Li ◽  
Ling Li

Background Colorectal cancer (CRC) is the third most common cancer in the world. The present study is aimed at identifying hub genes associated with the progression of CRC. Method The data of the patients with CRC were obtained from the Gene Expression Omnibus (GEO) database and assessed by weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses performed in R by WGCNA, several hub genes that regulate the mechanism of tumorigenesis in CRC were identified. Differentially expressed genes in the data sets GSE28000 and GSE42284 were used to construct a co-expression network for WGCNA. The yellow, black and blue modules associated with CRC level were filtered. Combining the co-expression network and the PPI network, 15 candidate hub genes were screened. Results After validation using the TCGA-COAD dataset, a total of 10 hub genes (MT1X, MT1G, MT2A, CXCL8, IL1B, CXCL5, CXCL11, IL10RA, GZMB, KIT) closely related to the progression of CRC were identified. The expressions of MT1G, CXCL8, IL1B, CXCL5, CXCL11 and GZMB in CRC tissues were higher than normal tissues (p-value < 0.05). The expressions of MT1X, MT2A, IL10RA and KIT in CRC tissues were lower than normal tissues (p-value < 0.05). Conclusions By combinating with a series of methods including GO enrichment analysis, KEGG pathway analysis, PPI network analysis and gene co-expression network analysis, we identified 10 hub genes that were associated with the progression of CRC.


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