Identification of hub genes and pathways associated with bladder cancer based on co-expression network analysis

Zhang, Dong‐Qing; Zhou, Chuanen; Chen, Shouzhen; Yang, Yongmei; Shi, Benkang

doi:10.3892/ol.2017.6267

Cited by 14 publications

(14 citation statements)

References 46 publications

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“…For example, the expression of TMEM185A (transmembrane protein 185A) was tended to be down-regulated clones among patients with stage III serous ovarian carcinoma 19. TMPRSS11E (transmembrane protease, serine 11E) could suppress esophageal squamous cell carcinoma development by sensitizing cells to apoptosis under an apoptotic stimulus through downregulating the EGFR/AKT signaling pathway 20, but recently was found significantly upregulated in urinary bladder cancer patients 21, which was consistent with our study outcomes.…”

Section: Discussionsupporting

confidence: 88%

A novel gene signature combination improves the prediction of overall survival in urinary bladder cancer

Chen¹,

Zhang²,

Shao³

et al. 2019

J. Cancer

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Objectives: Bladder carcinoma is a clinical heterogeneous disease, which is with significant variability of the prognosis and high risk of death. This revealed prominently the need to identify high-efficiency cancer characteristics to predict clinical prognosis.Methods: Gene expression profiles of 93 bladder tumor patients from Gene Expression Omnibus data sets was performed in this study, along with 408 bladder tumor patients retrieved from The Cancer Genome Atlas database. The relationship of gene signature and overall survival was analyzed in the training cohort (n = 46). The validation for that was performed in an internal validation cohort (n = 47) and an external validation cohort (n = 408).Results: Four genes (TMPRSS11E, SCEL, KRT78, TMEM185A) were identified by univariable and multivariable Cox regression analysis. According to a risk score on the bases on the four-gene signature, we grouped these patients in high-risk group and low-risk group with significantly different overall survival in the training series and successfully validated it in both the internal and external validation cohorts. Subsequent studies demonstrated that the four-gene expression risk score was independent of radical cystectomy stage, chemotherapy and lymph node status. Higher rates of FAT4 mutation and MACF1 mutation in bladder tumors with high risk score were found compared with tumors with low risk score. Gene set enrichment analysis revealed high-risk score was associated with some tumor progression and recurrence associated pathways.Conclusions: This four-gene risk score might have potential clinical implications in the selection of high-risk urinary bladder cancer patients for aggressive therapy. The selected four genes might become potential therapeutic targets and diagnostic markers for urinary bladder cancer.

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Section: Discussionsupporting

confidence: 88%

A novel gene signature combination improves the prediction of overall survival in urinary bladder cancer

Chen¹,

Zhang²,

Shao³

et al. 2019

J. Cancer

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“…Genes showing increased expression in this region include three different transmembrane protease serine 11 genes (TMPRSS11d, e and g). TMPRSS11e is associated with decreased survival in iUC patients [67,68] and has been identified as a primary hub gene in coexpression networks marking iUC tumor progression [69]. This family of transmembrane proteins has not been extensively studied in iUC and, based on these results, is worth further investigation.…”

Section: Discussionmentioning

confidence: 99%

RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors

et al. 2020

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Background: Invasive urothelial carcinoma (iUC) is highly similar between dogs and humans in terms of pathologic presentation, molecular subtypes, response to treatment and age at onset. Thus, the dog is an established and relevant model for testing and development of targeted drugs benefiting both canine and human patients. We sought to identify gene expression patterns associated with two primary types of canine iUC tumors: those that express a common somatic mutation in the BRAF gene, and those that do not. Methods: We performed RNAseq on tumor and normal tissues from pet dogs. Analysis of differential expression and clustering, and positional and individual expression was used to develop gene set enrichment profiles distinguishing iUC tumors with and without BRAFV595E mutations, as well as genomic regions harboring excessive numbers of dysregulated genes. Results: We identified two expression clusters that are defined by the presence/absence of a BRAFV595E (BRAFV600E in humans) somatic mutation. BRAFV595E tumors shared significantly more dysregulated genes than BRAF wild-type tumors, and vice versa, with 398 genes differentiating the two clusters. Key genes fall into clades of limited function: tissue development, cell cycle regulation, immune response, and membrane transport. The genomic site with highest number of dysregulated genes overall lies in a locus corresponding to human chromosome 8q24, a region frequently amplified in human urothelial cancers. Conclusions: These data identify critical sets of genes that are differently regulated in association with an activating mutation in the MAPK/ERK pathway in canine iUC tumors. The experiments also highlight the value of the canine system in identifying expression patterns associated with a common, shared cancer.

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“…Previous studies only identified differentially expressed genes (DEGs) based on one database and there was a lack of validation when using other databases (Jia et al, 2015). Although some studies had validated their results through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, researchers only identified hub genes by constructing a co-expression network (Zhang et al, 2017) or a protein–protein interaction (PPI) network (Bi et al, 2015). In this study, we not only constructed a PPI network of DEGs to pick out hub genes, but also innovatively constructed a random forest model to further narrow down the number of hub genes in the PPI network by using these genes as features and their expression levels as feature values.…”

Section: Introductionmentioning

confidence: 99%

Identification of Hub Genes Associated With Progression and Prognosis in Patients With Bladder Cancer

Yan

Guo

et al. 2019

Front. Genet.

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Given that most bladder cancers (BCs) are diagnosed in advanced stages with poor prognosis, this study aims to find novel biomarkers associated with the progression and prognosis in patients with BC. 1,779 differentially expressed genes (DEGs) between BC samples and normal bladder tissues were identified in total. Then, 24 DEGs were regarded as candidate hub genes by constructing a protein–protein interaction (PPI) network and a random forest model. Among them, six genes (BUB1B, CCNB1, CDK1, ISG15, KIF15, and RAD54L) were eventually identified by using five analysis methods (one-way Analysis of Variance analysis, spearman correlation analysis, distance correlation analysis, receiver operating characteristic curve, and expression values comparison), which were correlated with the progression and prognosis of BC. Moreover, the validation of hub genes was conducted based on GSE13507, Oncomine, and CBioPortal. Results of univariate Cox regression analysis showed that the expression levels of all the hub genes were influence features of overall survival (OS) and cancer specific survival (CSS) based on GSE13507, and we further established a six-gene signature based on the expression levels of the six genes and their Cox regression coefficients. This signature showed good potential for clinical application suggested by survival analysis (OS: Hazard Ratio = 0.484, 95%CI: 0.298–0.786; P = 0.0034; CSS: Hazard Ratio = 0.244, 95%CI: 0.121–0.493, P < 0.0001) and decision curve analysis. In conclusion, our study indicates that six hub genes have great predictive value for the prognosis and progression of BC and may contribute to the exploration of further basic and clinical research of BC.

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Identification of hub genes and pathways associated with bladder cancer based on co-expression network analysis

Cited by 14 publications

References 46 publications

A novel gene signature combination improves the prediction of overall survival in urinary bladder cancer

A novel gene signature combination improves the prediction of overall survival in urinary bladder cancer

RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors

Identification of Hub Genes Associated With Progression and Prognosis in Patients With Bladder Cancer

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