scholarly journals Significance and Mechanisms Analyses of RB1 Mutation in Bladder Cancer Disease Progression and Drug Selection by Bioinformatics Analysis

2021 ◽  
pp. 1-10
Author(s):  
Dingguo Zhang ◽  
Jinjun Tian ◽  
Qier Xia ◽  
Zhenyu Yang ◽  
Bin Gu
Keyword(s):  
Bladder Cancer ◽  
Disease Progression ◽  
Drug Sensitivity ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Drug Selection ◽  
Cancer Disease ◽  
Ezh2 Expression ◽  
Bladder Cancer Cells

BACKGROUND: Bladder cancer is still a disease of significant morbidity and mortality. In bladder cancer, RB1 is one of the most common mutant genes. METHODS: In this study, we explored the Genomics of Drug Sensitivity in Cancer (GDSC) database for drug sensitivity. The latest TCGA data were downloaded for analysis. To deal with functional enrichment analysis, GSEA, KEGG and GO were used. Prognostic analyses have been carried out using the GEPIA online tool. RESULTS: Results from the GDSC database showed that bladder cancer cells with RB1 mutation are more resistant to Dactolisib, MK-2206 and GNE-317. RB1 mutation was found in 25%bladder cancer patients. Patients with RB1 mutation often had lower RB1 mRNA expression level and higher histologic grade. In addition, we identified 999 differentially expressed genes in both groups. Functional enrichment analysis suggested that DEGs were primarily enriched in multiple metabolic progressions, cell proliferation and cancer related pathways. There were strong correlations between WT1, GPR37, CHRM2 and EZH2 expression levels and the prognosis. CONCLUSIONS: In all, the significance of RB1 mutation in disease progression and drug selection in bladder cancer was suggested by our results, and multiple genes and pathways related to such a program were identified.

scholarly journals Significance of TP53 mutation in bladder cancer disease progression and drug selection

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8261 ◽  
Author(s):  
Guang Wu ◽  
Fei Wang ◽  
Kai Li ◽  
Shugen Li ◽  
Chunchun Zhao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Disease Progression ◽  
Drug Sensitivity ◽  
Tp53 Mutation ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Advanced Tumor Stage ◽  
Drug Selection

Background The tumor protein p53 (TP53) mutant is one of the most frequent mutant genes in bladder cancer. In this study, we assessed the importance of the TP53 mutation in bladder cancer progression and drug selection, and identified potential pathways and core genes associated with the underlying mechanisms. Methods Gene expression data used in this study were downloaded from The Cancer Genome Atlas and cBioportal databases. Drug sensitivity data were obtained from the Genomics of Drug Sensitivity in Cancer. We did functional enrichment analysis by gene set enrichment analysis (GSEA) and the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results We found the TP53 mutation in 50% of bladder cancer patients. Patients with the TP53 mutation were associated with a lower TP53 mRNA expression level, more advanced tumor stage and higher histologic grade. Three drugs, mitomycin-C, doxorubicin and gemcitabine, were especially more sensitive to bladder cancer with the TP53 mutation. As for the mechanisms, we identified 863 differentially expressed genes (DEGs). Functional enrichment analysis suggested that DEGs were primarily enriched in multiple metabolic progressions, chemical carcinogenesis and cancer related pathways. The protein–protein interaction network identified the top 10 hub genes. Our results have suggested the significance of TP53 mutation in disease progression and drug selection in bladder cancer, and identified multiple genes and pathways related in such program, offering novel basis for bladder cancer individualized treatment.

scholarly journals An epithelial–mesenchymal transition-related long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Hang Tong ◽  
Tinghao Li ◽  
Shun Gao ◽  
Hubin Yin ◽  
Honghao Cao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Risk Groups ◽  
Functional Enrichment ◽  
Diagnostic Efficacy ◽  
Mesenchymal Transition

Abstract Bladder cancer is a common malignant tumour worldwide. Epithelial–mesenchymal transition (EMT)-related biomarkers can be used for early diagnosis and prognosis of cancer patients. To explore, accurate prediction models are essential to the diagnosis and treatment for bladder cancer. In the present study, an EMT-related long noncoding RNA (lncRNA) model was developed to predict the prognosis of patients with bladder cancer. Firstly, the EMT-related lncRNAs were identified by Pearson correlation analysis, and a prognostic EMT-related lncRNA signature was constructed through univariate and multivariate Cox regression analyses. Then, the diagnostic efficacy and the clinically predictive capacity of the signature were assessed. Finally, Gene set enrichment analysis (GSEA) and functional enrichment analysis were carried out with bioinformatics. An EMT-related lncRNA signature consisting of TTC28-AS1, LINC02446, AL662844.4, AC105942.1, AL049840.3, SNHG26, USP30-AS1, PSMB8-AS1, AL031775.1, AC073534.1, U62317.2, C5orf56, AJ271736.1, and AL139385.1 was constructed. The diagnostic efficacy of the signature was evaluated by the time-dependent receiver-operating characteristic (ROC) curves, in which all the values of the area under the ROC (AUC) were more than 0.73. A nomogram established by integrating clinical variables and the risk score confirmed that the signature had a good clinically predict capacity. GSEA analysis revealed that some cancer-related and EMT-related pathways were enriched in high-risk groups, while immune-related pathways were enriched in low-risk groups. Functional enrichment analysis showed that EMT was associated with abundant GO terms or signaling pathways. In short, our research showed that the 14 EMT-related lncRNA signature may predict the prognosis and progression of patients with bladder cancer.

scholarly journals Transcriptome-Wide Map of N6-Methyladenosine Methylome Profiling in Human Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Aolin Li ◽  
Ying Gan ◽  
Congcong Cao ◽  
Binglei Ma ◽  
Quan Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Gene Expression Pattern ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Rna Modification ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Normal Tissues ◽  
Cancer Tissues

N6-Methyladenosine (m6A) is the most widespread internal RNA modification in several species. In spite of latest advances in researching the biological roles of m6A, its function in the development and progression of bladder cancer remains unclear. In this study, we used MeRIPty -55-seq and RNA-seq methods to obtain a comprehensive transcriptome-wide m6A profiling and gene expression pattern in bladder cancer and paired normal adjacent tissues. Our findings showed that there were 2,331 hypomethylated and 3,819 hypermethylated mRNAs, 32 hypomethylated and 105 hypermethylated lncRNAs, and 15 hypomethylated and 238 hypermethylated circRNAs in bladder cancer tissues compared to adjacent normal tissues. Furthermore, m6A is most often harbored in the coding sequence (CDS), with some near the start and stop codons between two groups. Functional enrichment analysis revealed that differentially methylated mRNAs, lncRNAs, and circRNAs were mostly enriched in transcriptional misregulation in cancer and TNF signaling pathway. We also found that different m6A methylation levels of gene might regulate its expression. In summary, our results for the first time provide an m6A landscape of human bladder cancer, which expand the understanding of m6A modifications and uncover the regulation of mRNAs, lncRNAs, and circRNAs through m6A modification in bladder cancer.

scholarly journals Identification of a FLG-wide-type bladder cancer subtype with poor prognosis and prediction use in immune checkpoint

2021 ◽  
Author(s):  
Liang Chen ◽  
Liulin Xiong ◽  
Weinan Chen ◽  
Lizhe An ◽  
Huanrui Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Poor Prognosis ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Immune Biomarkers

Abstract Background Bladder cancer (BLCA) is one of most common urinary tract malignant tumor and immunotherapy have generated a great deal of interest in BLCA. Immune checkpoint blockade (ICB) therapy has significantly progressed the treatment of BLCA. Multiple studies have suggested that specific genetic mutations may serve as immune biomarkers for ICB therapy. Objective In this study, we aimed to investigate the role of mutations genes and subtypes in prognosis and immune checkpoint prediction in BLCA. Method Mutation information and expression profiles were acquired from The Cancer Genome Atlas (TCGA) database. Integrated bioinformatics analysis was carried out to explore the mutation genes of BLCA. Functional enrichment analysis Gene Ontology (GO) and Gene set enrichment analysis (GSEA) was conducted. The infiltrating immune cells and the prediction of ICB between different subtypes group were explored using immuCellAI algorithm. Results The mutation genes Filaggrin (FLG) gene were identified. Following the study on its subtypes and functional enrichment analysis, Sub2 of FLG-wide type was found to have relationships with poor prognosis and immune infiltration BLCA. What’s more, Sub2 of FLG-wide type may be used as a biomarker to predict the prognosis of BLCA patients receiving ICB. Conclusion This research provides a new basis and ideas for guiding the clinical application of BLCA immunotherapy.

scholarly journals Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 66 ◽  
Author(s):  
Chuan Zhang ◽  
Mandy Berndt-Paetz ◽  
Jochen Neuhaus
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Cell Movement ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Nodal Metastasis ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Protein Protein Interaction

Bladder cancer (BCa) is one of the most common malignancies and has a relatively poor outcome worldwide. However, the molecular mechanisms and processes of BCa development and progression remain poorly understood. Therefore, the present study aimed to identify candidate genes in the carcinogenesis and progression of BCa. Five GEO datasets and TCGA-BLCA datasets were analyzed by statistical software R, FUNRICH, Cytoscape, and online instruments to identify differentially expressed genes (DEGs), to construct protein‒protein interaction networks (PPIs) and perform functional enrichment analysis and survival analyses. In total, we found 418 DEGs. We found 14 hub genes, and gene ontology (GO) analysis revealed DEG enrichment in networks and pathways related to cell cycle and proliferation, but also in cell movement, receptor signaling, and viral carcinogenesis. Compared with noncancerous tissues, TPM1, CRYAB, and CASQ2 were significantly downregulated in BCa, and the other hub genes were significant upregulated. Furthermore, MAD2L1 and CASQ2 potentially play a pivotal role in lymph nodal metastasis. CRYAB and CASQ2 were both significantly correlated with overall survival (OS) and disease-free survival (DFS). The present study highlights an up to now unrecognized possible role of CASQ2 in cancer (BCa). Furthermore, CRYAB has never been described in BCa, but our study suggests that it may also be a candidate biomarker in BCa.

Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Wrky Transcription Factor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Callose Deposition ◽  
Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

scholarly journals Structural variations in papaya genomes

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenyang Liao ◽  
Xunxiao Zhang ◽  
Shengcheng Zhang ◽  
Zhicong Lin ◽  
Xingtan Zhang ◽  
...  
Keyword(s):  
Agronomic Traits ◽  
Enrichment Analysis ◽  
Copy Number Variant ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Structural Variations ◽  
Reproduction Traits ◽  
Depth Study ◽  
Environmental Adaptability ◽  
The Impact

Abstract Background Structural variations (SVs) are a type of mutations that have not been widely detected in plant genomes and studies in animals have shown their role in the process of domestication. An in-depth study of SVs will help us to further understand the impact of SVs on the phenotype and environmental adaptability during papaya domestication and provide genomic resources for the development of molecular markers. Results We detected a total of 8083 SVs, including 5260 deletions, 552 tandem duplications and 2271 insertions with deletion being the predominant, indicating the universality of deletion in the evolution of papaya genome. The distribution of these SVs is non-random in each chromosome. A total of 1794 genes overlaps with SV, of which 1350 genes are expressed in at least one tissue. The weighted correlation network analysis (WGCNA) of these expressed genes reveals co-expression relationship between SVs-genes and different tissues, and functional enrichment analysis shows their role in biological growth and environmental responses. We also identified some domesticated SVs genes related to environmental adaptability, sexual reproduction, and important agronomic traits during the domestication of papaya. Analysis of artificially selected copy number variant genes (CNV-genes) also revealed genes associated with plant growth and environmental stress. Conclusions SVs played an indispensable role in the process of papaya domestication, especially in the reproduction traits of hermaphrodite plants. The detection of genome-wide SVs and CNV-genes between cultivated gynodioecious populations and wild dioecious populations provides a reference for further understanding of the evolution process from male to hermaphrodite in papaya.

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