Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities

Abstract Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDSs). Patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization and a small-sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these 2 techniques. Microarray data were confirmed by gene amplification and flow cytometry using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. In trisomy 8, up-regulated genes were primarily involved in immune and inflammatory responses, and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis and apoptosis and down-regulation of genes controlling cell growth and differentiation. These results imply distinct molecular mechanisms for monosomy 7 and trisomy 8 MDS and implicate specific pathogenic pathways.

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NFκB-Mediated Up-Regulation of Transcription Factors Related to More Primitive State of Hematopoietic Progenitor Cells.

Blood ◽

10.1182/blood.v110.11.1246.1246 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1246-1246

Author(s):

Rodrigo A. Panepucci ◽

Lucila H.B. Oliveira ◽

Dalila L. Zanette ◽

Greice A. Molfetta ◽

Rita C.V. Carrara ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Progenitor Cells ◽

Real Time ◽

Quantitative Pcr ◽

Expression Profiles ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Cd34 Cells ◽

Primitive State

Abstract We have previously shown that a distinctive feature of umbilical cord blood (UCB) CD34+ hematopoietic progenitor cells (HSPC) as compared to bone marrow (BM) CD34+ is a higher expression of transcription targets and components of the nuclear factor kappa B (NF-κB) pathway. NFKB2 and RELB are sub-units of the transcription factor (TF) that specifically mediates the constitutive NF-κB signaling pathway and their increased levels could be related with the primitive state of the newborn’s HSPC. However, BM and UCB CD34+ HSPC differ in their sub-population compositions, and a higher proportion of more primitive cells among the CD34+ cells could account for those differences. CD133 is a surface marker expressed on a more primitive sub-population of CD34+ cells that are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells. We used flow cytometry, oligonucleotide microarray gene expression profiling and real time quantitative PCR to better characterize immunomagnetically sorted CD34+ and CD133+ HSPC derived from BM and UCB. We found that UCB CD34+ cells contain a larger proportion of CD133+ cells (around 70%), differing from BM CD34+ cells (around 30%). Cluster analysis of the expression profiles, encompassing 10.000 genes, showed that UCB CD133+ are more similar to UCB CD34+ than to BM CD133+ cells. Furthermore, a statistically significant higher expression of NFKB2 and RELB was demonstrated by quantitative PCR on UCB CD133+ HSPC, compared to BM. Overall this indicates that despite distinct compositions of the cells from UCB or BM, UCB HSPC display intrinsic molecular differences related to their ontological age. The comparison of the gene expression profiles of the CD133+ with the CD34+ populations revealed the higher expression of many well known factors related to more primitive HSPC and hemangioblasts. In fact, TFs such as RUNX1/AML1, GATA3, USF1, TAL1/SCL, HOXA9 and HOXB4 were all present at higher levels in CD133+ HSPC. In an attempt to identify a key TF that could be responsible for the expression of these important factors, we carried a promoter analysis for the set of highly expressed TF found in the CD133 cells. A frequency of TF binding sites significantly higher than the expected was observed for the NF-κB TFs, including potential NF-κB targets such as RUNX1, GATA3 and USF1. Measurements of GATA3, NFKB2 and RELB expression by real-time PCR showed a higher expression of the three genes in CD133+ samples (both from BM and UCB), as well as a correlation of the expression levels of NFkB2 and RELB with one another and with GATA3 (Sperman’s correlation), indicating that GATA3 could be, in fact, regulated by NF-κB. To further test this hypothesis, we used interference RNA (RNAi) against NFKB2 in HSPC. Levels of NFKB2, GATA3 and RELB (a known target of NFKB2/RELB dimmers) were down-modulated, in comparison with cells transfected with control RNAi. Taken together, our data indicates that constitutive NF-κB signaling may act up-regulating transcription factors related to a more primitive state of HSPC.

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Gene Expression Profiling of CD34+ Cells in Patients with Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v112.11.3642.3642 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3642-3642

Author(s):

Andrea Pellagatti ◽

Mario Cazzola ◽

Aristoteles Giagounidis ◽

Janet Perry ◽

Luca Malcovati ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Hierarchical Clustering ◽

Myelodysplastic Syndromes ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Differentially Expressed ◽

Good Separation ◽

Trisomy 8 ◽

Cd34 Cells

Abstract The myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic malignancies, characterized by blood cytopenias, ineffective hematopoiesis and a hypercellular bone marrow. We have investigated the gene expression profiles of a large group of patients with MDS in order to better understand the molecular pathogenesis of this disorder. The CD34+ cells obtained from 154 MDS patients and 17 healthy individuals were analyzed using Affymetrix U133 Plus2.0 arrays. 38 genes were up-regulated by >2-fold in at least 77 MDS patients, and pathway analysis using these genes showed that the interferon signalling pathway was significantly deregulated (p=0.0006). Indeed IFIT1, the most up-regulated gene (up-regulated in 110 of 154 MDS patients), is an interferon-stimulated gene (ISG). Other ISGs, which mediate growth inhibitory effects of interferon, such as IFITM1, IFI44L and IFIT3, were markedly up-regulated in the majority of MDS patients. Up-regulation of ISGs is a major feature of MDS and may be responsible for some of the hematological characteristics of this disorder, such as peripheral blood cytopenias. We investigated differences in gene expression that could distinguish MDS patients according to their FAB subtype classification (48 patients with RA, 44 patients with RARS and 62 patients with RAEB). Hierarchical clustering performed using the 773 significantly differentially expressed probe sets identified showed that MDS patients with RARS constitute the most homogeneous group, while MDS patients with RA and RAEB show more overlap. RARS gene expression profile was characterized by up-regulation of mitochondrial-related genes and by down-regulation of ABCB7, a gene mutated in the rare inherited X-linked sideroblastic anemia with ataxia (XLSA/A). Moreover, a good separation between the 20 patients with RARS and the 20 patients with RCMD-RS was obtained by hierarchical clustering using the 86 significantly differentially expressed genes between these two WHO subgroups. One of the most significant genes was MFN1, which is essential for mitochondrial fusion and maintenance of mitochondrial morphology. The association of distinct gene expression profiles with specific cytogenetic groups was also determined, and we were able to separate by hierarchical clustering MDS patients with del(5q), patients with −7/del(7q) and patients with trisomy 8. The expression profile of patients with the del(5q) was characterized by down-regulation of genes mapping to chromosome 5q. Genes differentially expressed in patients with −7/del(7q) include LOX and UBE2H, while genes differentially expressed in patients with trisomy 8 include HRSP12 and TPM4. These findings suggest distinct molecular pathogenetic pathways for MDS patients with del(5q), −7/del(7q) and trisomy 8. In order to identify differences in gene expression associated with MDS disease progression, we compared the 48 patients with early MDS (RA) and the 35 patients with advanced MDS (RAEB2). Hierarchical clustering performed using 1081 significantly differentially expressed probe sets resulted in a good separation between MDS patients with RA and patients with RAEB2. LEF1, a regulator of neutrophilic granulopoiesis, was the most significant differentially expressed gene with higher expression levels in patients with RA and decreasing in patients with RAEB2. Other genes showing higher expression levels in patients with RA, decreasing in patients with RAEB2, include CASC5, a cancer susceptibility candidate gene, and RBBP8, a gene that plays a role in DNA-damage-induced cell cycle checkpoint control. Several genes mapping to the cell cycle pathway were significantly deregulated between early and advanced MDS. This study provides new important insights into the pathophysiology of MDS and represents a first step towards determining pathway signatures in MDS as a guide to targeted therapies.

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A model of human p210bcr/ABL-mediated chronic myelogenous leukemia by transduction of primary normal human CD34+ cells with a BCR/ABL-containing retroviral vector

Blood ◽

10.1182/blood.v97.8.2406 ◽

2001 ◽

Vol 97 (8) ◽

pp. 2406-2412 ◽

Cited By ~ 62

Author(s):

Robert C. Zhao ◽

Yuehua Jiang ◽

Catherine M. Verfaillie

Keyword(s):

Cell Lines ◽

Chronic Myelogenous Leukemia ◽

Molecular Mechanisms ◽

Cell Model ◽

Fibroblast Cell ◽

Myelogenous Leukemia ◽

Hematopoietic Progenitor Cell ◽

Hematopoietic Progenitor ◽

Human Cd34 ◽

Cd34 Cells

Abstract Most insights into the molecular mechanisms underlying transformation by the p210BCR/ABL oncoprotein are derived from studies in which BCR/ABL cDNA was introduced into hematopoietic or fibroblast cell lines. However, such cell line models may not represent all the features of chronic myelogenous leukemia (CML) caused by additional genetic abnormalities and differences in the biology of cell lines compared with primary hematopoietic progenitor and stem cells. A primary human hematopoietic progenitor cell model for CML was developed by the transduction of b3a2 BCR/ABL cDNA in normal CD34+cells. Adhesion of BCR/ABL-transduced CD34+ cells to fibronectin was decreased, but migration over fibronectin was enhanced compared with that of mock-transduced CD34+ cells. Adhesion to fibronectin did not decrease the proliferation of BCR/ABL-transduced CD34+ cells but decreased the proliferation of mock-transduced CD34+ cells. This was associated with elevated levels of p27Kip in p210BCR/ABL-expressing CD34+ cells. In addition, the presence of p210BCR/ABLdelayed apoptosis after the withdrawal of cytokines and serum. Finally, significantly more and larger myeloid colony-forming units grew from BCR/ABL than from mock-transduced CD34+ cells. Thus, the transduction of CD34+ cells with the b3a2-BCR/ABL cDNA recreates most, if not all, phenotypic abnormalities seen in primary CML CD34+ cells. This model should prove useful for the study of molecular mechanisms associated with the presence of p210BCR/ABL in CML.

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Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

Pharmaceuticals ◽

10.3390/ph14010041 ◽

2021 ◽

Vol 14 (1) ◽

pp. 41

Author(s):

Hana Votavova ◽

Zuzana Urbanova ◽

David Kundrat ◽

Michaela Dostalova Merkerova ◽

Martin Vostry ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Blood Cell ◽

Myelodysplastic Syndrome ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Adaptive Immune Response ◽

Gene Expression Profiles ◽

Iron Chelator ◽

Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

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Pan-Cancer Transcriptional Models Predicting Chemosensitivity in Human Tumors

Cancer Informatics ◽

10.1177/11769351211002494 ◽

2021 ◽

Vol 20 ◽

pp. 117693512110024

Author(s):

Jason D Wells ◽

Jacqueline R Griffin ◽

Todd W Miller

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Human Tumors ◽

Molecular Characteristics ◽

Survival Times ◽

Chemotherapy Drugs ◽

Testing Dataset ◽

Cancer Models ◽

Cancer Types ◽

Pan Cancer

Motivation: Despite increasing understanding of the molecular characteristics of cancer, chemotherapy success rates remain low for many cancer types. Studies have attempted to identify patient and tumor characteristics that predict sensitivity or resistance to different types of conventional chemotherapies, yet a concise model that predicts chemosensitivity based on gene expression profiles across cancer types remains to be formulated. We attempted to generate pan-cancer models predictive of chemosensitivity and chemoresistance. Such models may increase the likelihood of identifying the type of chemotherapy most likely to be effective for a given patient based on the overall gene expression of their tumor. Results: Gene expression and drug sensitivity data from solid tumor cell lines were used to build predictive models for 11 individual chemotherapy drugs. Models were validated using datasets from solid tumors from patients. For all drug models, accuracy ranged from 0.81 to 0.93 when applied to all relevant cancer types in the testing dataset. When considering how well the models predicted chemosensitivity or chemoresistance within individual cancer types in the testing dataset, accuracy was as high as 0.98. Cell line–derived pan-cancer models were able to statistically significantly predict sensitivity in human tumors in some instances; for example, a pan-cancer model predicting sensitivity in patients with bladder cancer treated with cisplatin was able to significantly segregate sensitive and resistant patients based on recurrence-free survival times ( P = .048) and in patients with pancreatic cancer treated with gemcitabine ( P = .038). These models can predict chemosensitivity and chemoresistance across cancer types with clinically useful levels of accuracy.

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A Novel Regulatory Axis, CHD1L-MicroRNA 486-Matrix Metalloproteinase 2, Controls Spermatogonial Stem Cell Properties

Molecular and Cellular Biology ◽

10.1128/mcb.00357-18 ◽

2018 ◽

Vol 39 (4) ◽

Cited By ~ 2

Author(s):

Shan-Shan Liu ◽

Eithne Margaret Maguire ◽

Yin-Shan Bai ◽

Li Huang ◽

Yurong Liu ◽

...

Keyword(s):

Gene Expression ◽

Stem Cell ◽

Matrix Metalloproteinase ◽

Molecular Mechanisms ◽

Nuclear Translocation ◽

Expression Profiles ◽

Matrix Metalloproteinase 2 ◽

Small Rna Sequencing ◽

Growth Properties ◽

The Matrix

ABSTRACT Spermatogonial stem cells (SSCs) are unipotent germ cells that are at the foundation of spermatogenesis and male fertility. However, the underlying molecular mechanisms governing SSC stemness and growth properties remain elusive. We have recently identified chromodomain helicase/ATPase DNA binding protein 1-like (Chd1l) as a novel regulator for SSC survival and self-renewal, but how these functions are controlled by Chd1l remains to be resolved. Here, we applied high-throughput small RNA sequencing to uncover the microRNA (miRNA) expression profiles controlled by Chd1l and showed that the expression levels of 124 miRNA transcripts were differentially regulated by Chd1l in SSCs. KEGG pathway analysis shows that the miRNAs that are differentially expressed upon Chd1l repression are significantly enriched in the pathways associated with stem cell pluripotency and proliferation. As a proof of concept, we demonstrate that one of the most highly upregulated miRNAs, miR-486, controls SSC stemness gene expression and growth properties. The matrix metalloproteinase 2 (MMP2) gene has been identified as a novel miR-486 target gene in the context of SSC stemness gene regulation and growth properties. Data from cotransfection experiments showed that Chd1l, miR-486, and MMP2 work in concert in regulating SSC stemness gene expression and growth properties. Finally, our data also revealed that MMP2 regulates SSC stemness gene expression and growth properties through activating β-catenin signaling by cleaving N-cadherin and increasing β-catenin nuclear translocation. Our data demonstrate that Chd1l–miR-486–MMP2 is a novel regulatory axis governing SSC stemness gene expression and growth properties, offering a novel therapeutic opportunity for treating male infertility.

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Comparative RNA-Seq Analyses of Solenopsis japonica (Hymenoptera: Formicidae) Reveal Gene in Response to Cold Stress

Genes ◽

10.3390/genes12101610 ◽

2021 ◽

Vol 12 (10) ◽

pp. 1610

Author(s):

Mohammad Vatanparast ◽

Youngjin Park

Keyword(s):

Gene Expression ◽

Cold Stress ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Predatory Behavior ◽

P Value ◽

Molecular Response ◽

Rna Seq ◽

Protein Database ◽

Brood Chamber

Solenopsis japonica, as a fire ant species, shows some predatory behavior towards earthworms and woodlice, and preys on the larvae of other ant species by tunneling into a neighboring colony’s brood chamber. This study focused on the molecular response process and gene expression profiles of S. japonica to low (9 °C)-temperature stress in comparison with normal temperature (25 °C) conditions. A total of 89,657 unigenes (the clustered non-redundant transcripts that are filtered from the longest assembled contigs) were obtained, of which 32,782 were annotated in the NR (nonredundant protein) database with gene ontology (GO) terms, gene descriptions, and metabolic pathways. The results were 81 GO subgroups and 18 EggNOG (evolutionary genealogy of genes: Non-supervised Orthologous Groups) keywords. Differentially expressed genes (DEGs) with log2fold change (FC) > 1 and log2FC < −1 with p-value ≤ 0.05 were screened for cold stress temperature. We found 215 unigenes up-regulated and 115 unigenes down-regulated. Comparing transcriptome profiles for differential gene expression resulted in various DE proteins and genes, including fatty acid synthases and lipid metabolism, which have previously been reported to be involved in cold resistance. We verified the RNA-seq data by qPCR on 20 up- and down-regulated DEGs. These findings facilitate the basis for the future understanding of the adaptation mechanisms of S. japonica and the molecular mechanisms underlying the response to low temperatures.

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Transcriptome-wide gene expression plasticity in Stipa grandis in response to grazing intensity differences

10.22541/au.160655409.95797246/v1 ◽

2020 ◽

Author(s):

Zhenhua Dang ◽

Yuanyuan Jia ◽

Yunyun Tian ◽

Jiabin Li ◽

Yanan Zhang ◽

...

Keyword(s):

Gene Expression ◽

Metabolic Pathways ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Grazing Intensity ◽

Glycolate Oxidase ◽

Bisphosphate Carboxylase ◽

Grazing Intensities

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is one of the widespread dominant species on the typical steppe of the Inner Mongolian Plateau, and is regarded as a suitable species for studying the effects of grazing in this region. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Accordingly, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. A total of 2,357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified that indicated modulation of Calvin–Benson cycle and photorespiration metabolic pathways. The key gene´expression profiles encoding various proteins (e.g., Ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection, and identify important questions to address in future transcriptome studies.

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Insight into Molecular Profile Changes after Skeletal Muscle Contusion Using Microarray and Bioinformatics Analyses

10.21203/rs.3.rs-85830/v1 ◽

2020 ◽

Author(s):

Na Li ◽

Ru-feng Bai ◽

Chun Li ◽

Li-hong Dang ◽

Qiu-xiang Du ◽

...

Keyword(s):

Gene Expression ◽

Network Analysis ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Healing Process ◽

Differentially Expressed ◽

Molecular Profile ◽

Wound Age ◽

Functional Modules

Abstract Background: Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. This study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process.Methods: A total of 33 rats were divided randomly into control (n = 3), mild contusion (n = 15), and severe contusion (n = 15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n = 3 per subgroup). Then full genome microarray of RNA isolated from muscle tissue was performed to access the gene expression changes during healing process.Results: A total of 2,844 and 2,298 differentially expressed genes were identified in the mild and severe contusion groups, respectively. The analysis of the overlapping differentially expressed genes showed that there are common mechanisms of transcriptomic repair of mild and severe contusion within 48 h post-contusion. This was supported by the results of principal component analysis, hierarchical clustering, and weighted gene co‐expression network analysis of the 1,620 coexpressed genes in mildly and severely contused muscle. From these analyses, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. We then performed an analysis of the functions of genes (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation, and protein–protein interaction network analysis) in the functional modules and temporal clusters, and the hub genes in each module–cluster pair were identified. Interestingly, we found that genes downregulated within 24−48 h of the healing process were largely associated with metabolic processes, especially oxidative phosphorylation of reduced nicotinamide adenine dinucleotide phosphate, which has been rarely reported. Conclusions: These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation.

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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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