Potential genes and pathways associated with heterotopic ossification derived from analyses of gene expression profiles

Abstract Background Heterotopic ossification (HO) represents pathological lesions that refer to the development of heterotopic bone in extraskeletal tissues around joints. This study investigates the genetic characteristics of bone marrow mesenchymal stem cells (BMSCs) from HO tissues and explores the potential pathways involved in this ailment. Methods Gene expression profiles (GSE94683) were obtained from the Gene Expression Omnibus (GEO), including 9 normal specimens and 7 HO specimens, and differentially expressed genes (DEGs) were identified. Then, protein–protein interaction (PPI) networks and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for further analysis. Results In total, 275 DEGs were differentially expressed, of which 153 were upregulated and 122 were downregulated. In the biological process (BP) category, the majority of DEGs, including EFNB3, UNC5C, TMEFF2, PTH2, KIT, FGF13, and WISP3, were intensively enriched in aspects of cell signal transmission, including axon guidance, negative regulation of cell migration, peptidyl-tyrosine phosphorylation, and cell-cell signaling. Moreover, KEGG analysis indicated that the majority of DEGs, including EFNB3, UNC5C, FGF13, MAPK10, DDIT3, KIT, COL4A4, and DKK2, were primarily involved in the mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and Wnt signaling pathway. Ten hub genes were identified, including CX3CL1, CXCL1, ADAMTS3, ADAMTS16, ADAMTSL2, ADAMTSL3, ADAMTSL5, PENK, GPR18, and CALB2. Conclusions This study presented novel insight into the pathogenesis of HO. Ten hub genes and most of the DEGs intensively involved in enrichment analyses may be new candidate targets for the prevention and treatment of HO in the future.

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Potential Genes and Pathways Associated with Heterotopic Ossification, Derived from Analyses of Gene Expression Profiles

10.21203/rs.3.rs-572774/v1 ◽

2021 ◽

Author(s):

Zhanyu Yang ◽

Delong Liu ◽

Rui Guan ◽

Xin Li ◽

Yiwei Wang ◽

...

Keyword(s):

Gene Expression ◽

Protein Kinase ◽

Heterotopic Ossification ◽

Signaling Pathway ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Differentially Expressed ◽

Heterotopic Bone ◽

Hub Genes ◽

Ppi Networks

Abstract Background: Heterotopic ossification (HO) represents pathological lesions, referred to the development of heterotopic bone in extraskeletal tissues around joints. This study will investigate the genetic characteristics of bone marrow mesenchymal stem cells (BMSCs) from HO tissues and explore the potential pathways involved. Methods: The gene expression profiles (GSE94683) was obtained from the Gene Expression Omnibus (GEO), including 9 normal specimens and 7 HO specimens, and differentially expressed genes (DEGs) were identified. Then, the protein‑protein interaction (PPI) networks, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis were performed for further analysis. Results: Totally 275 DEGs were differentially expressed, of which 153 were upregulated and 122 were downregulated. In the biological process (BP), the majority of DEGs, including EFNB3, UNC5C, TMEFF2, PTH2, KIT, FGF13 and WISP3, were intensively enriched in cell signal transmission items, including axon guidance, negative regulation of cell migration, peptidyl-tyrosine phosphorylation and cell-cell signaling. Moreover, KEGG analysis indicated that the majority of DEGs, including EFNB3, UNC5C, FGF13, MAPK10, DDIT3, KIT, COL4A4 and DKK2, primarily involved in mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway and Wnt signaling pathway. 10 hub genes were identified, including CX3CL1, CXCL1, ADAMTS3, ADAMTS16, ADAMTSL2, ADAMTSL3, ADAMTSL5, PENK, GPR18, CALB2.Conclusions: This study presents a novel insight into the pathogenesis of HO. 10 hub genes and most of the DEGs intensively involved in enrichment analyses may be the new candidate targets for the prevention and treatment of HO in the future.

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Screening of Hub Genes Associated with Lung Adenocarcinoma by Integrated Bioinformatic Analysis

10.21203/rs.3.rs-580657/v1 ◽

2021 ◽

Author(s):

Zimeng Wei ◽

Min Zhao ◽

Linnan Zang

Keyword(s):

Gene Expression ◽

Lung Adenocarcinoma ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Analysis Tool ◽

Hub Genes ◽

Kegg Analysis ◽

Ppi Networks

Abstract Background Lung adenocarcinoma (LUAD) is the main histological subtype of lung cancer. However, the molecular mechanism underlying LUAD is not yet clearly defined, but elucidating this process in detail would be of great significance for clinical diagnosis and treatment. Methods Gene expression profiles were retrieved from Gene Expression Omnibus database (GEO), and the common differentially expressed genes (DEGs) were identified by online GEO2R analysis tool. Subsequently, the enrichment analysis of function and signaling pathways of DEGs in LUAD were performed by gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomics (KEGG) analysis. The protein-protein interaction (PPI) networks of the DEGs were established through the Search Tool for the Retrieval of Interacting Genes (STRING) database and hub genes were screened by plug-in CytoHubba in Cytoscape. Afterwards, we detected the expression of hub genes in LUAD and other cancers via GEPIA, Oncomine and HPA databases. Finally, Kaplan-Meier plotter were performed to analyze the prognosis efficacy of hub genes. Results 74 up-regulated and 238 down-regulated DEGs were identified. As for the up-regulated DEGs, KEGG analysis results revealed they were mainly enrolled in protein digestion and absorption. However, the down-regulated DEGs were primarily enriched in cell adhesion molecules. Subsequently, 9 hub genes: KIAA0101, CDCA7, TOP2A, CDC20, ASPM, TPX2, CENPF, UBE2T and ECT2, were identified and showed higher expression in both LUAD and other cancers. Finally, all these hub genes were found significantly related to the prognosis of LUAD (p < 0.05). Conclusions Our results screened out the hub genes and pathways that were related to the development and prognosis of LUAD, which could provide new insight for the future molecularly targeted therapy and prognosis evaluation of LUAD.

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Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Cancer Cell International ◽

10.1186/s12935-019-1080-y ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Cheng Zhang ◽

Bingye Zhang ◽

Di Meng ◽

Chunlin Ge

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Differentially Expressed Genes ◽

Expression Profiles ◽

Functional Enrichment ◽

Differentially Expressed ◽

Hub Genes ◽

Ppi Networks ◽

Differentially Methylated Genes ◽

Tumorigenesis And Progression

Abstract Background The incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis. Methods The gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein–protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database. Results We identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA. Conclusions Our study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.

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Identification of DMSA-Coated Fe3O4 Nanoparticles Induced-Apoptosis Response Genes in Human Monocytes by cDNA Microarrays

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.749.377 ◽

2013 ◽

Vol 749 ◽

pp. 377-383 ◽

Cited By ~ 3

Author(s):

Ying Xun Liu ◽

Jian Yuan Huang ◽

Dong Liang Wang ◽

Jin Ke Wang

Keyword(s):

Gene Expression ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Differentially Expressed ◽

Dependent Manner ◽

Receptor Signaling ◽

Apoptosis Pathway ◽

Receptor Signaling Pathway

This study investigated the cell apoptosis and gene expression profiles of human THP-1 monocytes in order to identify the molecular mechanism of cell apoptosis induced by meso-2,-3-dimercaptosuccinnic acid-coated Fe3O4magnetic nanoparticles. Cell apoptosis was visualized with flow cytometry after treated by 50 and 100 μg/ml Fe3O4nanoparticles, and the gene expression profiles were detected with Affymetrix Human Genome U133 Plus 2.0 GeneChips® microarrays. The transmission electron microscopy obserbation revealed that THP-1 cells were effectively labeled by the Fe3O4nanoparticles. The internalized Fe3O4nanoparticles increased cell apoptosis in a dose-dependent manner, but not decreased cell viability significantly. The cDNA microarray results showed that hundreds of genes were significantly regulated at the concentration of 50 and 100 μg/ml, and the level of these genes exhibited a dose response, includingCD14,CD86,CFLAR,IL-1,NFKBIA,NLRC4,NAIPandAIP3. The Fe3O4nanoparticles treatments resulted in significantly altered in Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and Cell apoptosis signaling pathway. Gene ontology analysis of these differentially expressed genes demonstrated that mainly up-regulated genes were related to cytokine production and cell apoptosis. These results showed that the Fe3O4nanoparticles induced THP-1 cells apoptosis and the level of lots of genes involved in extrinsic apoptosis pathway differentially expressed, which further revealed demonstrated the relation between Fe3O4MNPs treatment and cell apoptosis.

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An integrative bioinformatics analysis of microarray data for identifying hub genes as diagnostic biomarkers of preeclampsia

Bioscience Reports ◽

10.1042/bsr20190187 ◽

2019 ◽

Vol 39 (9) ◽

Cited By ~ 2

Author(s):

Keling Liu ◽

Qingmei Fu ◽

Yao Liu ◽

Chenhong Wang

Keyword(s):

Gene Expression ◽

Microarray Data ◽

Bioinformatics Analysis ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Support Vector ◽

Hub Genes ◽

Diagnostic Biomarkers

Abstract Preeclampsia (PE) is a disorder of pregnancy that is characterised by hypertension and a significant amount of proteinuria beginning after 20 weeks of pregnancy. It is closely associated with high maternal morbidity, mortality, maternal organ dysfunction or foetal growth restriction. Therefore, it is necessary to identify early and novel diagnostic biomarkers of PE. In the present study, we performed a multi-step integrative bioinformatics analysis of microarray data for identifying hub genes as diagnostic biomarkers of PE. With the help of gene expression profiles of the Gene Expression Omnibus (GEO) dataset GSE60438, a total of 268 dysregulated genes were identified including 131 up- and 137 down-regulated differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs suggested that DEGs were significantly enriched in disease-related biological processes (BPs) such as hormone activity, immune response, steroid hormone biosynthesis, metabolic pathways, and other signalling pathways. Using the STRING database, we established a protein–protein interaction (PPI) network based on the above DEGs. Module analysis and identification of hub genes were performed to screen a total of 17 significant hub genes. The support vector machines (SVMs) model was used to predict the potential application of biomarkers in PE diagnosis with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.958 in the training set and 0.834 in the test set, suggesting that this risk classifier has good discrimination between PE patients and control samples. Our results demonstrated that these 17 differentially expressed hub genes can be used as potential biomarkers for diagnosis of PE.

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4 Molecularly guided multiplexed digital spatial analysis reveals differential gene expression profiles in the WNT-β-catenin pathway between melanoma and prostate tumors

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0004 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A4-A4

Author(s):

Anushka Dikshit ◽

Dan Zollinger ◽

Karen Nguyen ◽

Jill McKay-Fleisch ◽

Kit Fuhrman ◽

...

Keyword(s):

Gene Expression ◽

Single Cell ◽

Single Molecule ◽

Spatial Information ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Fluorescence Assay ◽

Differentially Expressed ◽

Tumor Type ◽

Prostate Tumors

BackgroundThe canonical WNT-β-catenin signaling pathway is vital for development and tissue homeostasis but becomes strongly tumorigenic when dysregulated. and alter the transcriptional signature of a cell to promote malignant transformation. However, thorough characterization of these transcriptomic signatures has been challenging because traditional methods lack either spatial information, multiplexing, or sensitivity/specificity. To overcome these challenges, we developed a novel workflow combining the single molecule and single cell visualization capabilities of the RNAscope in situ hybridization (ISH) assay with the highly multiplexed spatial profiling capabilities of the GeoMx™ Digital Spatial Profiler (DSP) RNA assays. Using these methods, we sought to spatially profile and compare gene expression signatures of tumor niches with high and low CTNNB1 expression.MethodsAfter screening 120 tumor cores from multiple tumors for CTNNB1 expression by the RNAscope assay, we identified melanoma as the tumor type with the highest CTNNB1 expression while prostate tumors had the lowest expression. Using the RNAscope Multiplex Fluorescence assay we selected regions of high CTNNB1 expression within 3 melanoma tumors as well as regions with low CTNNB1 expression within 3 prostate tumors. These selected regions of interest (ROIs) were then transcriptionally profiled using the GeoMx DSP RNA assay for a set of 78 genes relevant in immuno-oncology. Target genes that were differentially expressed were further visualized and spatially assessed using the RNAscope Multiplex Fluorescence assay to confirm GeoMx DSP data with single cell resolution.ResultsThe GeoMx DSP analysis comparing the melanoma and prostate tumors revealed that they had significantly different gene expression profiles and many of these genes showed concordance with CTNNB1 expression. Furthermore, immunoregulatory targets such as ICOSLG, CTLA4, PDCD1 and ARG1, also demonstrated significant correlation with CTNNB1 expression. On validating selected targets using the RNAscope assay, we could distinctly visualize that they were not only highly expressed in melanoma compared to the prostate tumor, but their expression levels changed proportionally to that of CTNNB1 within the same tumors suggesting that these differentially expressed genes may be regulated by the WNT-β-catenin pathway.ConclusionsIn summary, by combining the RNAscope ISH assay and the GeoMx DSP RNA assay into one joint workflow we transcriptionally profiled regions of high and low CTNNB1 expression within melanoma and prostate tumors and identified genes potentially regulated by the WNT- β-catenin pathway. This novel workflow can be fully automated and is well suited for interrogating the tumor and stroma and their interactions.GeoMx Assays are for RESEARCH ONLY, not for diagnostics.

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Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

Human Genomics ◽

10.1186/s40246-020-00293-1 ◽

2020 ◽

Vol 14 (1) ◽

Author(s):

Fatemeh Khodabandehloo ◽

Sara Taleahmad ◽

Reza Aflatoonian ◽

Farzad Rajaei ◽

Zahra Zandieh ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Signaling Pathway ◽

Expression Profiles ◽

Wnt Signaling Pathway ◽

Hub Genes ◽

Gene Expressions ◽

Cell Based Therapy ◽

Wnt Pathways ◽

Key Pathways

Abstract Background Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0. Results Gene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE. Conclusions These findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT.

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Bioinformatics analysis of differentially expressed genes and pathways in the development of cervical cancer

BMC Cancer ◽

10.1186/s12885-021-08412-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Baojie Wu ◽

Shuyi Xi

Keyword(s):

Gene Expression ◽

Cervical Cancer ◽

Differentially Expressed Genes ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Molecular Targets ◽

Enrichment Analysis ◽

Ppi Network ◽

Hub Genes ◽

Kegg Pathways

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.

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Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Hashimoto’s Thyroiditis

10.21203/rs.3.rs-1023446/v1 ◽

2021 ◽

Author(s):

Li Guoquan ◽

Du Junwei ◽

He Qi ◽

Fu Xinghao ◽

Ji Feihong ◽

...

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Inflammatory Responses ◽

Expression Profiles ◽

Treatment Options ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Chronic Lymphocytic Thyroiditis ◽

Hub Genes

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.

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

10.21203/rs.3.rs-595148/v1 ◽

2021 ◽

Author(s):

Hongpeng Fang ◽

Zhansen Huang ◽

Xianzi Zeng ◽

Jiaming Wan ◽

Jieying Wu ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Gene Expression Omnibus ◽

Transcriptional Level ◽

Hub Genes ◽

Kaplan Meier ◽

High Form

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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