scholarly journals SMC4, CCNB1 and CKS1B as potential targets and new critical biomarkers for the prognosis of human bladder cancer

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.

2022 ◽  
Vol 2022 ◽  
pp. 1-17
Author(s):  
Md. Rakibul Islam ◽  
Lway Faisal Abdulrazak ◽  
Mohammad Khursheed Alam ◽  
Bikash Kumar Paul ◽  
Kawsar Ahmed ◽  
...  

Background. Medulloblastoma (MB) is the most occurring brain cancer that mostly happens in childhood age. This cancer starts in the cerebellum part of the brain. This study is designed to screen novel and significant biomarkers, which may perform as potential prognostic biomarkers and therapeutic targets in MB. Methods. A total of 103 MB-related samples from three gene expression profiles of GSE22139, GSE37418, and GSE86574 were downloaded from the Gene Expression Omnibus (GEO). Applying the limma package, all three datasets were analyzed, and 1065 mutual DEGs were identified including 408 overexpressed and 657 underexpressed with the minimum cut-off criteria of ∣ log   fold   change ∣ > 1 and P < 0.05 . The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways enrichment analyses were executed to discover the internal functions of the mutual DEGs. The outcomes of enrichment analysis showed that the common DEGs were significantly connected with MB progression and development. The Search Tool for Retrieval of Interacting Genes (STRING) database was used to construct the interaction network, and the network was displayed using the Cytoscape tool and applying connectivity and stress value methods of cytoHubba plugin 35 hub genes were identified from the whole network. Results. Four key clusters were identified using the PEWCC 1.0 method. Additionally, the survival analysis of hub genes was brought out based on clinical information of 612 MB patients. This bioinformatics analysis may help to define the pathogenesis and originate new treatments for MB.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shilong You ◽  
Jiaqi Xu ◽  
Boquan Wu ◽  
Shaojun Wu ◽  
Ying Zhang ◽  
...  

Hypertensive nephropathy (HN), mainly caused by chronic hypertension, is one of the major causes of end-stage renal disease. However, the pathogenesis of HN remains unclarified, and there is an urgent need for improved treatments. Gene expression profiles for HN and normal tissue were obtained from the Gene Expression Omnibus database. A total of 229 differentially co-expressed genes were identified by weighted gene co-expression network analysis and differential gene expression analysis. These genes were used to construct protein–protein interaction networks to search for hub genes. Following validation in an independent external dataset and in a clinical database, POLR2I, one of the hub genes, was identified as a key gene related to the pathogenesis of HN. The expression level of POLR2I is upregulated in HN, and the up-regulation of POLR2I is positively correlated with renal function in HN. Finally, we verified the protein levels of POLR2I in vivo to confirm the accuracy of our analysis. In conclusion, our study identified POLR2I as a key gene related to the pathogenesis of HN, providing new insights into the molecular mechanisms underlying HN.


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 ◽  
Author(s):  
Huatian Luo ◽  
Da-qiu Chen ◽  
Jing-jing Pan ◽  
Zhang-wei Wu ◽  
Can Yang ◽  
...  

Abstract Background: Pancreatic cancer has many pathologic types, among which pancreatic ductal adenocarcinoma (PDAC) is the most common one. Bioinformatics has become a very common tool for the selection of potentially pathogenic genes. Methods: Three data sets containing the gene expression profiles of PDAC were downloaded from the gene expression omnibus (GEO) database. The limma package of R language was utilized to explore the differentially expressed genes (DEGs). To analyze functions and signaling pathways, the Database Visualization and Integrated Discovery (DAVID) was used. To visualize the protein-protein interaction (PPI) of the DEGs ,Cytoscape was performed under the utilization of Search Tool for the Retrieval of Interacting Genes (STRING). With the usage of the plug-in cytoHubba in cytoscape software, the hub genes were found out. To verify the expression levels of hub genes, Gene Expression Profiling Interactive Analysis (GEPIA) was performed. Last but not least, UALCAN analysis online tool was implemented to analyze the overall survival. Results: The 376 DEGs were highly enriched in biological processes including signal transduction, apoptotic process and several pathways, mainly associated with Protein digestion and absorption and Pancreatic secretion pathway. The expression levels of nucleolar and spindle associated protein 1 (NUSAP1) and SHC binding and spindle associated 1 (SHCBP1) were discovered highly expressed in pancreatic ductal adenocarcinoma tissues. NUSAP1 and SHCBP1 had a high correlation with prognosis. Conclusions: The findings of this bioinformatics analysis indicate that NUSAP1 and SHCBP1 may be key factors in the prognosis and treatment of pancreatic cancer.


2019 ◽  
Vol 47 (9) ◽  
pp. 4051-4058
Author(s):  
Wenbin Wu ◽  
Keyou You ◽  
Jinchan Zhong ◽  
Zhanwei Ruan ◽  
Bubu Wang

Objective The present study aimed to elucidate the underlying pathogenesis of Kawasaki disease (KD) and to identify potential biomarkers for KD. Methods Gene expression profiles for the GSE68004 dataset were downloaded from the Gene Expression Omnibus database. The pathways and functional annotations of differentially expressed genes (DEGs) in KD were examined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. Protein–protein interactions of the above-described DEGs were investigated using the Search Tool for the Retrieval of Interacting Genes (STRING). Results Gene Ontology analysis revealed that DEGs in KD were significantly enriched in biological processes, including the inflammatory response, innate immune response, defense response to Gram-positive bacteria, and antibacterial humoral response. In addition, 10 hub genes with high connectivity were selected from among these DEGs ( ITGAM, MPO, MAPK14, SLC11A1, HIST2H2BE, ELANE, CAMP, MMP9, NTS, and HIST2H2AC). Conclusion The identification of several novel hub genes in KD enhances our understanding of the molecular mechanisms underlying the progression of this disease. These genes may be potential diagnostic biomarkers and/or therapeutic molecular targets in patients with KD. ITGAM inhibitors in particular may be potential targets for KD therapy.


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.


2021 ◽  
Author(s):  
Xizi Sun

Abstract Esophageal squamous cell carcinoma (ESCC) is the most common type of human esophageal cancer with high mortality due to late stage diagnosis. Efforts have been made to figure out the genetic events underlying its carcinogenesis and progression, but the molecular mechanisms of these processes remain elusive. To identify the candidate genes involved in ESCC, literature about significantly mutated genes (SMGs) was extensively reviewed and gene expression profiles of GSE161533, GSE20347 and GSE77861 were downloaded from the Gene Expression Omnibus (GEO) database. Following the identification of 230 differentially expressed genes (DEGs), hub gene identification was performed by the plug-in MCODE in Cytoscape software. 14 hub genes were identified which were enriched in cell cycle, DNA replication and p53 signaling pathway. In summary, genes mentioned in this study may provide potential targets for treatment and diagnosis of ESCC and help us better understand the pathogenesis and progression of ESCC from genetic perspective.


2020 ◽  
Author(s):  
Xiao-Qing Lu ◽  
Jia-qian Zhang ◽  
Jun Qiao ◽  
Sheng-Xiao Zhang ◽  
Meng-Ting Qiu ◽  
...  

Abstract Background: Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy.Methods: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytoHubba plugin. Their prognostic values were assessed by Kaplan–Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. Results: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients.Discussion: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Weitie Wang ◽  
Tiance Wang ◽  
Yong Wang ◽  
Hulin Piao ◽  
Bo Li ◽  
...  

Thoracic aortic dissection (TAD) is a catastrophic disease worldwide, but the pathogenic genes and pathways are largely unclear. This study aims at integrating two gene expression profile datasets and verifying hub genes and pathways involved in TAD as well as exploring potential molecular mechanisms. We will combine our mRNAs expression profile (6 TAD tissues versus 6 non-TAD tissues) and GSE52093 downloaded from the Gene Expression Omnibus (GEO) database. The two mRNAs expression profiles contained 13 TAD aortic tissues and 11 non-TAD tissues. The two expression profile datasets were integrated and we found out coexpression of differentially expressed genes (DEGs) using bioinformatics methods. The gene ontology and pathway enrichment of DEGs were performed by DAVID and Kyoto Encyclopedia of Genes and Genomes online analyses, respectively. The protein-protein interaction networks of the DEGs were constructed according to the data from the STRING database. Cytohubber calculating result shows the top 10 hub genes with CDC20, AURKA, RFC4, MCM4, TYMS, MCM2, DLGAP5, FANCI, BIRC5, and POLE2. Module analysis revealed that TAD was associated with significant pathways including cell cycle, vascular smooth muscle contraction, and adrenergic signaling in cardiomyocytes. The qRT-PCR result showed that the expression levels of all the hub genes were significantly increased in OA samples (p < 0.05), and these candidate genes could be used as potential diagnostic biomarkers and therapeutic targets of TAD.


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