scholarly journals Bioinformatics Analysis of Some Novel Potential Biomarkers Associated With Osteoarthritis and Nervous System

Author(s):  
Zhongkui Guo ◽  
Yong Qin ◽  
Yang Chen ◽  
Yi Li ◽  
Ya Gu ◽  
...  

Abstract BackgroundOsteoarthritis (OA) is an age-related chronic inflammatory and degenerative changes that carries heavy burden for individuals and the society. The specific mechanism of OA still remains unclear today, which requires new methods and technologies to achieve some new breakthrough. Bioinformatics technology is a novel method to extract genetic information from many diseases. In this study, we aims at screening out some key genes to help to illuminate the pathogenesis of OA to help to diagnosis and cure it.Objective and MethodsBioinformatics technology was used to screen some key target genes that were closely related to OA and nervous system, and by using qRT-PCR to preliminary verify the results.ResultsIn this work, we analysis three gene expression profiles, GSE114007, GSE51588, and GSE55457, that downloaded from the Gene Expression Omnibus database (GEO). At last, a total of 878 DEGs were identified with dataset GSE114007 (P<0.05 and |logFC|>1.5), consisting of 495 up-regulated genes and 383 down-regulated genes between the osteoarthritis and normal cartilage tissues. And by combining with the screened results of GSE51588 and GSE55457, finally, three genes, HES1, JUN, and IRE2, which were closely correlated with the nervous system that may help to diagnosis and cure osteoarthritis in the future were identified, and the result of qRT-PCR preliminary confirmed our finding.ConclusionHES1, JUN, and IRE2 were three potential genes related to osteoarthritis and nervous system that may help to diagnosis and cure OA.

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhiqiang Wang ◽  
Zhongjun Ding ◽  
Yan Guan ◽  
Chunhui Liu ◽  
Linjun Wang ◽  
...  

Background. The molecular mechanism of nonobstructive azoospermia (NOA) remains unclear. The aim of this study was to identify gene expression changes in NOA patients and to explore potential biomarkers and therapeutic targets. Methods. The gene expression profiles of GSE45885 and GSE145467 were collected from the Gene Expression Omnibus (GEO) database, and the differences between NOA and normal spermatogenesis were analyzed. Enrichment analysis was performed to explore biological functions for common differentially expressed genes (DEGs) in GSE45885 and GSE145467. Coexpression analysis of DEGs in GSE45885 was performed, and two modules with the highest correlation with NOA were screened. Key genes were then screened from the intersection genes of the two modules and common DEGs and PPI network. The expression of key genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR) experiments. Finally, through miRTarBase, miRDB, and RAID, the miRNAs were predicted to regulate key genes, respectively. Results. A total of 345 common DEGs were identified and they were mainly related to spermatogenesis, insulin signaling pathway. Coexpression analysis of DEGs in GSE45885 yielded eight modules; MEblack and MEturquoise had the highest correlation with NOA. Six genes in MEturquoise and RNF141 in MEblack were identified as key genes. qRT-PCR experiments validated the differential expression of key genes between NOA and control. Furthermore, RNF141 was regulated by the largest number of miRNAs. Conclusion. Our findings suggest that the significant change expression of key genes may be potential markers and therapeutic targets of NOA and may have some impact on the development of NOA.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10468
Author(s):  
Kai Zhang ◽  
Kuikui Jiang ◽  
Ruoxi Hong ◽  
Fei Xu ◽  
Wen Xia ◽  
...  

Background Tamoxifen resistance in breast cancer is an unsolved problem in clinical practice. The aim of this study was to determine the potential mechanisms of tamoxifen resistance through bioinformatics analysis. Methods Gene expression profiles of tamoxifen-resistant MCF-7/TR and MCF-7 cells were acquired from the Gene Expression Omnibus dataset GSE26459, and differentially expressed genes (DEGs) were detected with R software. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. A protein–protein interaction (PPI) network was generated, and we analyzed hub genes in the network with the Search Tool for the Retrieval of Interacting Genes database. Finally, we used siRNAs to silence the target genes and conducted the MTS assay. Results We identified 865 DEGs, 399 of which were upregulated. GO analysis indicated that most genes are related to telomere organization, extracellular exosomes, and binding-related items for protein heterodimerization. PPI network construction revealed that the top 10 hub genes—ACLY, HSPD1, PFAS, GART, TXN, HSPH1, HSPE1, IRAS, TRAP1, and ATIC—might be associated with tamoxifen resistance. Consistently, RT-qPCR analysis indicated that the expression of these 10 genes was increased in MCF-7/TR cells comparing with MCF-7 cells. Four hub genes (TXN, HSPD1, HSPH1 and ATIC) were related to overall survival in patients who accepted tamoxifen. In addition, knockdown of HSPH1 by siRNA may lead to reduced growth of MCF-7/TR cell with a trend close to significance (P = 0.07), indicating that upregulation of HSPH1 may play a role in tamoxifen resistance. Conclusion This study revealed a number of critical hub genes that might serve as therapeutic targets in breast cancer resistant to tamoxifen and provided potential directions for uncovering the mechanisms of tamoxifen resistance.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiao-Qing Lu ◽  
Jia-Qian Zhang ◽  
Sheng-Xiao Zhang ◽  
Jun Qiao ◽  
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. Conclusions 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.


2020 ◽  
Author(s):  
Xiaoqing Guan ◽  
Zhiyuan Guan ◽  
Jiafu Ji ◽  
Chunli Song

Abstract Background : Osteosarcoma (OS) is the most common malignant tumor of bone which was featured with osteoid or immature bone produced by the malignant cells, and biomarkers are urgently needed to identify patients with this aggressive disease. Methods : We downloaded gene expression profiles from Gene Expression Omnibus (GEO) and The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) datasets for OS, respectively, and performed weighted gene co-expression network analysis (WGCNA) to identify the key module. Whereafter, functional annotation and Gene Set Enrichment Analysis (GSEA) demonstrated the relationships between target genes and OS. Results : In this study, we discovered four key genes – ALOX5AP, HLA-DMB, HLA-DRA and SPINT2 as new prognostic markers and confirmed their relationship with OS metastasis in the validation set. Conclusions : Overall, our work may shed light on the roles of ALOX5AP, HLA-DMB, HLA-DRA and SPINT2, thus providing valuable clues to investigate the metastasis of OS and corroborating the potential clinical application value of the 4-gene signature to some extent.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.


2021 ◽  
pp. 1-6
Author(s):  
Reza Vafaee ◽  
Mostafa Rezaei Tavirani ◽  
Sina Rezaei Tavirani ◽  
Mohammadreza Razzaghi

There are many documents about benefits of exercise on human health. However, evidences indicate to positive effect of exercise on disease prevention, understanding of many aspects of this mechanism need more investigations. Determination of critical genes which effect human health. GSE156249 including 12 gene expression profiles of healthy individual biopsy from vastus lateralis muscle before and after 12-week combined exercise training intervention were extracted from gene expression omnibus (GEO) database. The significant DEGs were included in interactome unit by Cytoscape software and STRING database. The network was analyzed to find the central nodes subnetwork clusters. The nodes of prominent cluster were assessed via gene ontology by using ClueGO. Number of 8 significant DEGs and 100 first neighbors analyzed via network analysis. The network includes 2 clusters and COL3A1, BGN, and LOX were determined as central DEGs. The critical DEGs were involved in cancer prevention process.


2021 ◽  
Vol 288 (1945) ◽  
pp. 20202793
Author(s):  
Alexander Yermanos ◽  
Daniel Neumeier ◽  
Ioana Sandu ◽  
Mariana Borsa ◽  
Ann Cathrin Waindok ◽  
...  

Neuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer's disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system. Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor and T cell receptor repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system of aged male mice. Furthermore, many of these B cells were of the IgM and IgD isotypes, and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.


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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