scholarly journals Identification of Novel Hub Genes Through Expression Profiles Analysis in Adrenocortical Carcinoma

2020 ◽  
Author(s):  
Chenhe Yao ◽  
Xiaoling Zhao ◽  
Xuemeng Shang ◽  
Binghan Jia ◽  
Shuaijie Dou ◽  
...  

Abstract Background: Adrenocortical carcinoma (ACC) is a heterogeneous and rare malignant tumor associated with a poor prognosis. The molecular mechanisms of ACC remain elusive and more accurate biomarkers for the prediction of prognosis are needed.Methods: In this study, integrative profiling analyses were performed to identify novel hub genes in ACC to provide promising targets for future investigation. Three gene expression profiling datasets in the GEO database were used for the identification of overlapped differentially expressed genes (DEGs) following the criteria of adj.P.Value<0.05 and |log2 FC|>0.5 in ACC. Novel hub genes were screened out following a series of processes: the retrieval of DEGs with no known associations with ACC on Pubmed, then the cross-validation of expression values and significant associations with overall survival in the GEPIA2 and starBase databases, and finally the prediction of gene-tumor association in the GeneCards database.Results: Four novel hub genes were identified and two of them, TPX2 and RACGAP1, were positively correlated with the staging. Interestingly, co-expression analysis revealed that the association between TPX2 and RACGAP1 was the strongest and that the expression of HOXA5 was almost completely independent of that of RACGAP1 and TPX2. Furthermore, the PPI network consisting of four novel genes and seed genes in ACC revealed that HOXA5, TPX2, and RACGAP1 were all associated with TP53. Conclusions: This study identified four novel hub genes (TPX2, RACHAP1, HXOA5 and FMO2) that may play crucial roles in the tumorigenesis and the prediction of prognosis of ACC.

2021 ◽  
Vol 24 (5-6) ◽  
pp. 267-279
Author(s):  
Xianyang Zhu ◽  
Wen Guo

<b><i>Background:</i></b> This study aimed to screen and validate the crucial genes involved in osteoarthritis (OA) and explore its potential molecular mechanisms. <b><i>Methods:</i></b> Four expression profile datasets related to OA were downloaded from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) from 4 microarray patterns were identified by the meta-analysis method. The weighted gene co-expression network analysis (WGCNA) method was used to investigate stable modules most related to OA. In addition, a protein-protein interaction (PPI) network was built to explore hub genes in OA. Moreover, OA-related genes and pathways were retrieved from Comparative Toxicogenomics Database (CTD). <b><i>Results:</i></b> A total of 1,136 DEGs were identified from 4 datasets. Based on these DEGs, WGCNA further explored 370 genes included in the 3 OA-related stable modules. A total of 10 hub genes were identified in the PPI network, including <i>AKT1</i>, <i>CDC42</i>, <i>HLA-DQA2</i>, <i>TUBB</i>, <i>TWISTNB</i>, <i>GSK3B</i>, <i>FZD2</i>, <i>KLC1</i>, <i>GUSB</i>, and <i>RHOG</i>. Besides, 5 pathways including “Lysosome,” “Pathways in cancer,” “Wnt signaling pathway,” “ECM-receptor interaction” and “Focal adhesion” in CTD and enrichment analysis and 5 OA-related hub genes (including <i>GSK3B, CDC42, AKT1, FZD2</i>, and <i>GUSB</i>) were identified. <b><i>Conclusion:</i></b> In this study, the meta-analysis was used to screen the central genes associated with OA in a variety of gene expression profiles. Three OA-related modules (green, turquoise, and yellow) containing 370 genes were identified through WGCNA. It was discovered through the gene-pathway network that <i>GSK3B, CDC42, AKT1, FZD2</i>, <i>and GUSB</i> may be key genes related to the progress of OA and may become promising therapeutic targets.


Open Medicine ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. 124-134
Author(s):  
Yin-yin Peng ◽  
Hong-bin Zhang ◽  
Xin Wang ◽  
Qing Xiao ◽  
Shu-liang Guo

Abstract Gene expression profiling studies have shown the pathogenetic role of oncogenic pathways in extranodal natural killer/T-cell lymphoma (ENKL). In this study, we aimed to identify the microRNAs (miRNAs) playing potential roles in ENKL, and to evaluate the genes and biological pathways associated to them. Gene expression profiles of ENKL patients were acquired from the gene expression omnibus (GEO) database. Most differentially expressed (DE)-miRNAs were identified in ENKL patients using limma package. Gene targets of the DE-miRNAs were collected from online databases (miRDB, miRWalk, miRDIP, and TargetScan), and used in Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses on Database for annotation, visualization, and integrated discovery database, and then used in protein–protein interaction (PPI) analysis on STRING database. Hub genes of the PPI network were identified in cytoHubba, and were evaluated in Biological networks gene ontology. According to the series GSE31377 and GSE43958 from GEO database, four DE-miRNAs were screened out: hsa-miR-363-3p, hsa-miR-296-5p, hsa-miR-155-5p, and hsa-miR-221-3p. Totally 164 gene targets were collected from the online databases, and used in the GO and KEGG pathway analyses and PPI network analysis. Ten hub genes of the PPI network were identified: AURKA, TP53, CDK1, CDK2, CCNB1, PLK1, CUL1, ESR1, CDC20, and PIK3CA. Those hub genes, as well as their correlative pathways, may be of diagnostic or therapeutic potential for ENKL, but further clinical evidence is still expected.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 623.1-623
Author(s):  
C. Wang ◽  
S. X. Zhang ◽  
S. Song ◽  
J. Qiao ◽  
R. Zhao ◽  
...  

Background:Nephritis is one of the predominant causes of morbidity and mortality in patients with lupus1 2.The lack of understanding regarding the molecular mechanisms of lupus nephritis(LN) hinders the development of specific targeted therapy for this progressive disease3.Objectives:In this study, we use bioinformatics method to analyze the genes involved in regulating the potential pathogenesis of LN.Methods:The expression profile of LN(GSE104948 and GSE32591) was obtained from the GEO database.GSE104948 was a memory chip, which included 32 LN glomerular biopsy tissues and 3 glomerular tissues from living donors.GSE32591 dataset included 32 LN glomerular biopsy tissues and 15 glomerular tissues from living donors. The Oligo package was used to process the data to obtain the expression matrix files of all the related genes.P<0.05 and |log2(FC)|>2 were setted as cut-off criteria for the DEGs.Ggplot2, heatmap packages were used to DEGs visualization. Metascape online tool was used to annotating DEGs for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis performed.We used STRING online database to construct protein-protein interaction (PPI) network. Hub genes were identified by Cytoscape.Results:In differential expression analysis,357 DEGs were identified,including 248 up-regulated genes and 109 down-regulated genes (Figure 1A,B).GO enrichment showed that these DEGs were primarily enriched in biological pathways, cell localization and molecular function and revealed that LN-related genes mainly involved in immune response.KEGG pathway annotation enrichment analysis revealed these DEGs were closely associated with Staphylococcus aureus infection,Complement and coagulation cascades (Figure 1D). Fourteen hub genes(IFT3,IRF7,OAS3,GBP2,RSAD2,MX1,IFIT2,IFI6,MX2,ISF15,IFIT1,QAS2,OASL,OAS1) were identified from PPI network (Figure 1C,E).Conclusion:Illuminating the molecular mechanisms of LN was help for deep understanding of LN.References:[1]Song J, Zhao L, Li Y. Comprehensive bioinformatics analysis of mRNA expression profiles and identification of a miRNA-mRNA network associated with lupus nephritis. Lupus 2020;29(8):854-61. doi: 10.1177/0961203320925155 [published Online First: 2020/05/22].[2]Yao F, Sun L, Fang W, et al. HsamiR3715p inhibits human mesangial cell proliferation and promotes apoptosis in lupus nephritis by directly targeting hypoxiainducible factor 1alpha. Mol Med Rep 2016;14(6):5693-98. doi: 10.3892/mmr.2016.5939 [published Online First: 2016/11/24].[3]Dall’Era M. Treatment of lupus nephritis: current paradigms and emerging strategies. Curr Opin Rheumatol 2017;29(3):241-47. doi: 10.1097/BOR.0000000000000381 [published Online First: 2017/02/17].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared


2021 ◽  
Author(s):  
Xu Chen ◽  
Yi Tang ◽  
Shen Chen ◽  
Wen-Hua Ling ◽  
Qing Wang

Background and aims: Non-alcoholic fatty liver disease (NAFLD) has become a common chronic liver disease in the world. Simple steatosis is the early phase of NAFLD. However, the molecular mechanisms underlying the development of steatosis have not yet been fully elucidated. Methods: Two public datasets (GSE48452 and GSE89632) through the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs) in the development of steatosis. A total of 72 participants including 38 normal histological controls and 34 simple steatosis patients were included in this study. GO, KEGG and PPI network analysis were performed to explore the function of DEGs. The results were further confirmed in high-fat diet (HFD)-fed mice and oleate-treated HepG2 cells. Results: Total 57 DEGs including 31 up- and 26 down-regulated genes between simple steatosis patients and healthy controls were determined. GO and KEGG analysis showed that most of DEGs were enriched in the ligand-receptor signaling pathways. PPI network construction was used to identify the hub genes of the DEGs. MYC, ANXA2, GDF15, AGTR1, NAMPT, LEPR, IGFBP-2, IL1RN, MMP7 and APLNR were identified as hub genes. And IGFBP-2 expression was found to be reversely associated with hepatic steatosis, fasting insulin, HOMA-IR index and ALT levels. In HFD-fed mice, hepatic IGFBP-2 was also downregulated and negatively associated with hepatic triglyceride levels. Moreover, overexpression IGFBP-2 ameliorated the oleate induced accumulation of triglycerides in hepatocytes. Conclusions: This study identified novel gene signatures in the hepatic steatosis and will provide new understanding and molecular clues of hepatic steatosis.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6092 ◽  
Author(s):  
Ping Yan ◽  
Yingchun He ◽  
Kexin Xie ◽  
Shan Kong ◽  
Weidong Zhao

Background Understanding hub genes involved in gastric cancer (GC) metastasis could lead to effective approaches to diagnose and treat cancer. In this study, we aim to identify the hub genes and investigate the underlying molecular mechanisms of GC. Methods To explore potential therapeutic targets for GC,three expression profiles (GSE54129, GSE33651, GSE81948) of the genes were extracted from the Gene Expression Omnibus (GEO) database. The GEO2R online tool was applied to screen out differentially expressed genes (DEGs) between GC and normal gastric samples. Database for Annotation, Visualization and Integrated Discovery was applied to perform Gene Ontology (GO) and KEGG pathway enrichment analysis. The protein-protein interaction (PPI) network of these DEGs was constructed using a STRING online software. The hub genes were identified by the CytoHubba plugin of Cytoscape software. Then, the prognostic value of these identified genes was verified by gastric cancer database derived from Kaplan-Meier plotter platform. Results A total of 85 overlapped upregulated genes and 44 downregulated genes were identified. The majority of the DEGs were enriched in extracellular matrix organization, endodermal cell differentiation, and endoderm formation. Moreover, five KEGG pathways were significantly enriched, including ECM-receptor interaction, amoebiasis, AGE-RAGE signaling pathway in diabetic complications, focal adhesion, protein digestion and absorption. By combining the results of PPI network and CytoHubba, a total of nine hub genes including COL1A1, THBS1, MMP2, CXCL8, FN1, TIMP1, SPARC, COL4A1, and ITGA5 were selected. The Kaplan-Meier plotter database confirmed that overexpression levels of these genes were associated with reduced overall survival, except for THBS1 and CXCL8. Conclusions Our study suggests that COL1A1, MMP2, FN1, TIMP1, SPARC, COL4A1, and ITGA5 may be potential biomarkers and therapeutic targets for GC. Further study is needed to assess the effect of THBS1 and CXCL8 on GC.


2020 ◽  
Author(s):  
Wenqiong Qin ◽  
Qiang Yuan ◽  
Yi Liu ◽  
Ying Zeng ◽  
Dandan Ke ◽  
...  

Abstract Background Ovarian tumors are the most malignant tumors of all gynecological tumors, and although multiple efforts have been made to elucidate the pathogenesis, the molecular mechanisms of ovarian cancer remain unclear. Methods In this study, we used bioinformatics to identify genes involved in the carcinogenesis and progression of ovarian cancer. Three microarray datasets (GSE14407, GSE29450, and GSE54388) were downloaded from Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified. For a more in-depth understanding of the DEGs, functional and pathway enrichment analyses were performed and a protein-protein interaction (PPI) network was constructed. The associated transcriptional factor (TFs) regulation network of the DEGs was also constructed. Kaplan Meier-plotter, Gene Expression Profiling Interactive Analysis (GEPIA), the Human Protein Atlas (HPA) database and the Oncomine database were implemented to validated hub genes. Results A total of 514 DEGs were detected after the analysis of the three gene expression profiles, including 171 upregulated and 343 downregulated genes. Nine hub genes ( CCNB1, CDK1, BUB1, CDC20, CCNA2, BUB1B, AURKA, RRM2, TTK) were obtained from the PPI network. Survival analysis showed that high expression levels of seven hub genes ( CCNB1, BUB1, BUB1B, CCNA2, AURKA, CDK1, and RRM2) were associated with worse overall survival (OS). All of seven hub genes were discovered highly expressed in ovarian cancer samples compared to normal ovary samples in GEPIA. Immunostaining results from the HPA database suggested that the expressions of CCNB1, CCNA2, AURKA, and CDK1 proteins were increased in ovarian cancer tissues, and Oncomine analysis indicated that the expression patterns of BUB1B, CCNA2, AURKA, CCNB1, CDK1, and BUB1 have associated with patient clinicopathological information. From the gene-transcriptional factor network, key transcriptional factors, such as POLR2A, ZBTB11, KLF9, and ELF1, were identified with close interactions with these hub genes. Conclusion We identified six significant DEGs with poor prognosis in ovarian cancer, which could be of potential biomarkers for ovarian cancer patients.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Baojie Wu ◽  
Shuyi Xi

Abstract Background This study aimed to explore and identify key genes and signaling pathways that contribute to the progression of cervical cancer to improve prognosis. Methods Three gene expression profiles (GSE63514, GSE64217 and GSE138080) were screened and downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) were screened using the GEO2R and Venn diagram tools. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Gene set enrichment analysis (GSEA) was performed to analyze the three gene expression profiles. Moreover, a protein–protein interaction (PPI) network of the DEGs was constructed, and functional enrichment analysis was performed. On this basis, hub genes from critical PPI subnetworks were explored with Cytoscape software. The expression of these genes in tumors was verified, and survival analysis of potential prognostic genes from critical subnetworks was conducted. Functional annotation, multiple gene comparison and dimensionality reduction in candidate genes indicated the clinical significance of potential targets. Results A total of 476 DEGs were screened: 253 upregulated genes and 223 downregulated genes. DEGs were enriched in 22 biological processes, 16 cellular components and 9 molecular functions in precancerous lesions and cervical cancer. DEGs were mainly enriched in 10 KEGG pathways. Through intersection analysis and data mining, 3 key KEGG pathways and related core genes were revealed by GSEA. Moreover, a PPI network of 476 DEGs was constructed, hub genes from 12 critical subnetworks were explored, and a total of 14 potential molecular targets were obtained. Conclusions These findings promote the understanding of the molecular mechanism of and clinically related molecular targets for cervical cancer.


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):  
Nana Yang ◽  
Qianghua Wang ◽  
Biao Ding ◽  
Yinging Gong ◽  
Yue Wu ◽  
...  

Abstract Background: The accumulation of ROS resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation likely plays important role in PE pathogenesis. This study aims to investigate expression profiles and functions of the ferroptosis-related genes (FRGs) in early- and late-onset preeclampsia.Methods: The gene expression data and clinical information were downloaded from GEO database. The “limma” R package was used for screening differentially expressed genes. GO(Gene Ontology), Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative real-time reverse transcriptase PCR was used to verify the expression of hub FRGs in PE.Results: A total number of 4,215 DEGs were identified between EOPE and preterm cases and 3,356 DEGs were found between EOPE and LOPE subtypes. 20 significantly different FRGs were identified in EOPE, while only 3 in LOPE. Functional enrichment analysis revealed that the differentially expressed FRGs was mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as response to hypoxia, iron homeostasis and iron ion binding process. The PPI network analysis and verification by RT-qPCR resulted in the identification of the following six interesting FRGs: FTH1, HIF1A, FTL, IREB2, MAPK8 and PLIN2. Conclusions: EOPE and LOPE owned distinct underlying molecular mechanisms and ferroptosis may be mainly implicated in pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.


2021 ◽  
Author(s):  
Hongpeng Fang ◽  
Zhansen Huang ◽  
Xianzi Zeng ◽  
Jiaming Wan ◽  
Jieying Wu ◽  
...  

Abstract Background As a common malignant cancer of the urinary system, the precise molecular mechanisms of bladder cancer remain to be illuminated. The purpose of this study was to identify core genes with prognostic value as potential oncogenes for the diagnosis, prognosis or novel therapeutic targets of bladder cancer. Methods The gene expression profiles GSE3167 and GSE7476 were available from the Gene Expression Omnibus (GEO) database. Next, PPI network was built to filter the hub gene through the STRING database and Cytoscape software and GEPIA and Kaplan-Meier plotter were implemented. Frequency and type of hub genes and sub groups analysis were performed in cBioportal and ULCAN database. Finally,We used RT-qPCR to confirm our results. Results Totally, 251 DEGs were excavated from two datasets in our study. We only founded high expression of SMC4, TYMS, CCNB1, CKS1B, NUSAP1 and KPNA2 was associated with worse outcomes in bladder cancer patients and no matter from the type of mutation or at the transcriptional level of hub genes, the tumor showed a high form of expression. However, only the expression of SMC4,CCNB1and CKS1B remained changed between the cancer and the normal samples in our results of RT-qPCR. Conclusion In conclusion,These findings indicate that the SMC4,CCNB1 and CKS1B may serve as critical biomarkers in the development and poor prognosis.


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