scholarly journals Bioinformatics Analysis Identifying Key Biomarkers in Bladder Cancer

Data ◽  
2020 ◽  
Vol 5 (2) ◽  
pp. 38
Author(s):  
Chuan Zhang ◽  
Mandy Berndt-Paetz ◽  
Jochen Neuhaus

Our goal was to find new diagnostic and prognostic biomarkers in bladder cancer (BCa), and to predict molecular mechanisms and processes involved in BCa development and progression. Notably, the data collection is an inevitable step and time-consuming work. Furthermore, identification of the complementary results and considerable literature retrieval were requested. Here, we provide detailed information of the used datasets, the study design, and on data mining. We analyzed differentially expressed genes (DEGs) in the different datasets and the most important hub genes were retrieved. We report on the meta-data information of the population, such as gender, race, tumor stage, and the expression levels of the hub genes. We include comprehensive information about the gene ontology (GO) enrichment analyses and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. We also retrieved information about the up- and down-regulation of genes. All in all, the presented datasets can be used to evaluate potential biomarkers and to predict the performance of different preclinical biomarkers in BCa.

2021 ◽  
Vol 11 ◽  
Author(s):  
Rui Sun ◽  
Simin Li ◽  
Ke Zhao ◽  
Mei Diao ◽  
Long Li

BackgroundThis study aimed to systematically investigate gene signatures for hepatoblastoma (HB) and identify potential biomarkers for its diagnosis and treatment.Materials and MethodsGSE131329 and GSE81928 were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between hepatoblastoma and normal samples were identified using the Limma package in R. Then, the similarity of network traits between two sets of genes was analyzed by weighted gene correlation network analysis (WGCNA). Cytoscape was used to visualize and select hub genes. PPI network of hub genes was construed by Cytoscape. GO enrichment and KEGG pathway analyses of hub genes were carried out using ClueGO. The random forest classifier was constructed based on the hub genes using the GSE131329 dataset as the training set, and its reliability was validated using the GSE81928 dataset. The resulting core hub genes were combined with the InnateDB database to identify the innate core genes.ResultsA total of 4244 DEGs in HB were identified. WGCNA identified four modules that were significantly correlated with the disease status. A total of 114 hub genes were obtained within the top 20 genes of each node rank. 6982 relation pairs and 3700 nodes were contained in the PPI network of 114 hub genes. GO enrichment and KEGG pathway analyses of hub genes were focused on MAPK, cell cycle, p53, and other crucial pathways involved in HB. A random forest classifier was constructed using the 114 hub genes as feature genes, resulting in a 95.5% true positive rate when classifying HB and normal samples. A total of 35 core hub genes were obtained through the mean decrease in accuracy and mean decrease Gini of the random forest model. The classification efficiency of the random forest model was 81.4%. Finally, CDK1, TOP2A, ADRA1A, FANCI, XRCC1, TPX2, CCNB2, CDK4, GLYATL1, and CFHR3 were identified by cross-comparison with the InnateDB database.ConclusionOur study established a random forest classifier that identified 10 core genes in HB. These findings may be beneficial for the diagnosis, prediction, and targeted therapy of HB.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 622.2-623
Author(s):  
T. Kong ◽  
S. X. Zhang ◽  
S. Song ◽  
X. Sun ◽  
C. Zheng ◽  
...  

Background:Primary Sjögren’s syndrome (pSS) is an autoimmune disease that featured as lymphoplasmacytic infiltration of the exocrine glands leading to sicca symptoms1. However, its underlying molecular mechanisms remain elusive.Objectives:This study aims to identify differentially expressed genes (DEGs) and pathways associated with the progression of pSS using bioinformatics analysis and explore its pathogenesis.Methods:The pSS-associated gene chip data set GSE66795 was obtained from the Gene Expression Omnibus (GEO) database, which included 131 cases of fully-phenotyped pSS patients’ whole blood samples and 29 cases of control samples. DEGs were screened Using R software. Online tool Metascape2 was used to make Gene Ontology (GO) and KEGG pathway enrichment. The PPI network was performed using String database. Hub genes were identified by Cytoscape.Results:A total of 108 DEGs were captured, including 101 up-regulated genes and 7 down-regulated genes. GO enrichment showed that these DEGs were primarily enriched in defense response to virus, response to interferon-gamma, regulation of innate immune response, response to interferon-beta, double-stranded RNA binding, response to interferon-alpha. KEGG pathway enrichment analysis showed these DEGs were principally enriched in Influenza A, RIG-I-like receptor signaling pathway, necroptosis, Staphylococcus aureus infection. Finally, 9 hub genes (STAT1, IRF7, OAS2, GBP1, OAS1, IFIT3, IFIH1, OAS3, DDX60) had highest degree value.Conclusion:The findings identified molecular mechanisms and the key hub genes that may involve in the occurrence and development of pSS.References:[1]Francois H, Mariette X. Renal involvement in primary Sjogren syndrome. Nat Rev Nephrol 2016;12(2):82-93. doi: 10.1038/nrneph.2015.174 [published Online First: 2015/11/17].[2]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].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 ◽  
Vol 49 (7) ◽  
pp. 030006052110295
Author(s):  
Yunfei Zhang ◽  
Yue Huang ◽  
Wen-xia Chen ◽  
Zheng-min Xu

Objective This study aimed to explore the potential molecular mechanism of allergic rhinitis (AR) and identify gene signatures by analyzing microarray data using bioinformatics methods. Methods The dataset GSE19187 was used to screen differentially expressed genes (DEGs) between samples from patients with AR and healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied for the DEGs. Subsequently, a protein–protein interaction (PPI) network was constructed to identify hub genes. GSE44037 and GSE43523 datasets were screened to validate critical genes. Results A total of 156 DEGs were identified. GO analysis verified that the DEGs were enriched in antigen processing and presentation, the immune response, and antigen binding. KEGG analysis demonstrated that the DEGs were enriched in Staphylococcus aureus infection, rheumatoid arthritis, and allograft rejection. PPI network and module analysis predicted seven hub genes, of which six ( CD44, HLA-DPA1, HLA-DRB1, HLA-DRB5, MUC5B, and CD274) were identified in the validation dataset. Conclusions Our findings suggest that hub genes play important roles in the development of AR.


2021 ◽  
Author(s):  
Jing Cao ◽  
Zhaoya Liu ◽  
Jie Liu ◽  
Chan Li ◽  
Guogang Zhang ◽  
...  

Abstract BackgroundIschemic cardiomyopathy (ICM) is considered to be the common cause of heart failure, which has high prevalence and mortality. This study aimed to investigate the different expressed genes (DEGs) and pathways in the pathogenesis of ICM using bioinformatics analysis.MethodsThe control and ICM datasets GSE116250,GSE46224 and GSE5406 were collected from the gene expression omnibus (GEO) database. DEGs were identified using limma package of R software and co-expressed genes were identified with Venn diagrams. Then, the gene otology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explored the biological functions and signaling pathways. Protein-protein interaction (PPI) networks were assembled with Cytoscape software to identify hub genes related to the pathogenesis of ICM.ResultsA total of 844 DEGs were screened from GSE116250, of which 447 up-regulated and 397 down-regulated genes respectively. A total of 99 DEGs were singled out from GSE46224, of which 58 up-regulated and 41 down-regulated genes respectively. 30 DEGs were screened from GSE5406, including 10 genes with up-regulated expression and 20 genes with down-regulated expression. 5 up-regulated and 3 down-regulated co-expressed DEGs were intersected in three datasets. GO and KEGG pathway analyses revealed that DEGs mainly enriched in collagen fibril organization, protein digestion and absorption, AGE-RAGE signaling pathway and other related pathways. Collagen alpha-1(III) chain (COL3A1), collagen alpha-2(I) chain (COL1A2) and lumican (LUM) are the three hub genes in all three datasets through PPI network analysis. The expression of 5 DEGs (SERPINA3, FCN3, COL3A1, HBB, MXRA5) in heart tissues by qRT-PCR results were consistent with our GEO analysis, while expression of 3 DEGs (ASPN, LUM, COL1A2) were opposite with GEO analysis.ConclusionsThese findings from this bioinformatics network analysis investigated key hub genes, which contributed to better understand the mechanism and new therapeutic targets of ICM.


Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Haoming Li ◽  
Linqing Zou ◽  
Jinhong Shi ◽  
Xiao Han

Abstract Background Alzheimer’s disease (AD) is a fatal neurodegenerative disorder, and the lesions originate in the entorhinal cortex (EC) and hippocampus (HIP) at the early stage of AD progression. Gaining insight into the molecular mechanisms underlying AD is critical for the diagnosis and treatment of this disorder. Recent discoveries have uncovered the essential roles of microRNAs (miRNAs) in aging and have identified the potential of miRNAs serving as biomarkers in AD diagnosis. Methods We sought to apply bioinformatics tools to investigate microarray profiles and characterize differentially expressed genes (DEGs) in both EC and HIP and identify specific candidate genes and pathways that might be implicated in AD for further analysis. Furthermore, we considered that DEGs might be dysregulated by miRNAs. Therefore, we investigated patients with AD and healthy controls by studying the gene profiling of their brain and blood samples to identify AD-related DEGs, differentially expressed miRNAs (DEmiRNAs), along with gene ontology (GO) analysis, KEGG pathway analysis, and construction of an AD-specific miRNA–mRNA interaction network. Results Our analysis identified 10 key hub genes in the EC and HIP of patients with AD, and these hub genes were focused on energy metabolism, suggesting that metabolic dyshomeostasis contributed to the progression of the early AD pathology. Moreover, after the construction of an miRNA–mRNA network, we identified 9 blood-related DEmiRNAs, which regulated 10 target genes in the KEGG pathway. Conclusions Our findings indicated these DEmiRNAs having the potential to act as diagnostic biomarkers at an early stage of AD.


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.


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.


2020 ◽  
Author(s):  
Praveenkumar Devarbhavi ◽  
Basavaraj Vastrad ◽  
Anandkumar Tengli ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti

AbstractNeuroendocrine tumor (NET) is one of malignant cancer and is identified with high morbidity and mortality rates around the world. With indigent clinical outcomes, potential biomarkers for diagnosis, prognosis and drug target are crucial to explore. The aim of this study is to examine the gene expression module of NET and to identify potential diagnostic and prognostic biomarkers as well as to find out new drug target. The differentially expressed genes (DEGs) identified from GSE65286 dataset was used for pathway enrichment analyses and gene ontology (GO) enrichment analyses and protein - protein interaction (PPI) analysis and module analysis. Moreover, miRNAs and transcription factors (TFs) that regulated the up and down regulated genes were predicted. Furthermore, validation of hub genes was performed. Finally, molecular docking studies were performed. DEGs were identified, including 453 down regulated and 459 up regulated genes. Pathway and GO enrichment analysis revealed that DEGs were enriched in sucrose degradation, creatine biosynthesis, anion transport and modulation of chemical synaptic transmission. Important hub genes and target genes were identified through PPI network, modules, target gene - miRNA network and target gene - TF network. Finally, survival analyses, receiver operating characteristic (ROC) curve and RT-PCR validated the significant difference of ATP1A1, LGALS3, LDHA, SYK, VDR, OBSL1, KRT40, WWOX, NINL and PPP2R2B between metastatic NET and normal controls. In conclusion, the DEGs and hub genes with their regulatory elements identified in this study will help us understand the molecular mechanisms underlying NET and provide candidate targets for future research.


2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Weiwei Liang ◽  
FangFang Sun

Abstract This research was carried out to reveal specific hub genes involved in diabetic heart failure, as well as remarkable pathways that hub genes locate. The GSE26887 dataset from the GEO website was downloaded. The gene co-expression network was generated and central modules were analyzed to identify key genes using the WGCNA method. Functional analyses were conducted on genes of the clinical interest modules via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene ontology (GO) enrichment, associated with protein–protein interaction (PPI) network construction in a sequence. Centrality parameters of the PPI network were determined using the CentiScape plugin in Cytoscape. Key genes, defined as genes in the ≥95% percentile of the degree distribution of significantly perturbed networks, were identified. Twenty gene co-expression modules were detected by WGCNA analysis. The module marked in light yellow exhibited the most significant association with diabetes (P=0.08). Genes involved in this module were primarily located in immune response, plasma membrane and receptor binding, as shown by the GO analysis. These genes were primarily assembled in endocytosis and phagosomes for KEGG pathway enrichment. Three key genes, STK39, HLA-DPB1 and RAB5C, which may be key genes for diabetic heart failure, were identified. To our knowledge, our study is the first to have constructed the co-expression network involved in diabetic heart failure using the WGCNA method. The results of the present study have provided better understanding the molecular mechanism of diabetic heart failure.


2021 ◽  
pp. 1-11
Author(s):  
Yinan Chai ◽  
Lihan Xu ◽  
Rui He ◽  
Liangjun Zhong ◽  
Yuying Wang

BACKGROUND: Pulmonary metastasis is the most frequent cause of death in osteosarcoma (OS) patients. Recently, several bioinformatics studies specific to pulmonary metastatic osteosarcoma (PMOS) have been applied to identify genetic alterations. However, the interpretation and reliability of the results obtained were limited for the independent database analysis. OBJECTIVE: The expression profiles and key pathways specific to PMOS remain to be comprehensively explored. Therefore, in our study, three original datasets of GEO database were selected. METHODS: Initially, three microarray datasets (GSE14359, GSE14827, and GSE85537) were downloaded from the GEO database. Differentially expressed genes (DEGs) between PMOS and nonmetastatic osteosarcoma (NMOS) were identified and mined using DAVID. Subsequently, GO and KEGG pathway analyses were carried out for DEGs. Corresponding PPI network of DEGs was constructed based on the data collected from STRING datasets. The network was visualized with Cytoscape software, and ten hub genes were selected from the network. Finally, survival analysis of these hub genes also used the TARGET database. RESULTS: In total, 569 upregulated and 1238 downregulated genes were filtered as DEGs between PMOS and NMOS. Based on the GO analysis result, these DEGs were significantly enriched in the anatomical structure development, extracellular matrix, biological adhesion, and cell adhesion terms. Based on the KEGG pathway analysis result, these DEGs were mainly enriched in the pathways in cancer, PI3K-Akt signaling, MAPK signaling, focal adhesion, cytokine-cytokine receptor interaction, and IL-17 signaling. Hub genes (ANXA1 and CXCL12) were significantly associated with overall survival time in OS patient. CONCLUSION: Our results may provide new insight into pulmonary metastasis of OS. However, experimental studies remain necessary to elucidate the biological function and mechanism underlying PMOS.


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