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

Overview

Journal Bladder Cancer

Publisher IOS Press

Date 2024 Jul 12

PMID 38994537

Authors

Dingguo Zhang

Jinjun Tian

Qier Xia

Zhenyu Yang

Bin Gu

Affiliations

Soon will be listed here.

Abstract

Background: Bladder cancer is still a disease of significant morbidity and mortality. In bladder cancer, 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 mutation are more resistant to Dactolisib, MK-2206 and GNE-317. mutation was found in 25%bladder cancer patients. Patients with mutation often had lower 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.

Citing Articles

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References

Peyressatre M, Prevel C, Pellerano M, Morris M . Targeting cyclin-dependent kinases in human cancers: from small molecules to Peptide inhibitors. Cancers (Basel). 2015; 7(1):179-237. PMC: 4381256. DOI: 10.3390/cancers7010179. View

Vanden Heuvel J, Maddox E, Maalouf S . Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells. Elife. 2018; 7. PMC: 5760202. DOI: 10.7554/eLife.29747. View

Dyson N . RB1: a prototype tumor suppressor and an enigma. Genes Dev. 2016; 30(13):1492-502. PMC: 4949322. DOI: 10.1101/gad.282145.116. View

Dennis Jr G, Sherman B, Hosack D, Yang J, Gao W, Lane H . DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003; 4(5):P3. View

Kaufman D, Shipley W, Feldman A . Bladder cancer. Lancet. 2009; 374(9685):239-49. DOI: 10.1016/S0140-6736(09)60491-8. View

Morris E, Ji J, Yang F, Di Stefano L, Herr A, Moon N . E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8. Nature. 2008; 455(7212):552-6. PMC: 3148807. DOI: 10.1038/nature07310. View

Cerami E, Gao J, Dogrusoz U, Gross B, Sumer S, Aksoy B . The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2(5):401-4. PMC: 3956037. DOI: 10.1158/2159-8290.CD-12-0095. View

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

Sternberg C, Donat S, Bellmunt J, Millikan R, Stadler W, De Mulder P . Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. Urology. 2007; 69(1 Suppl):62-79. DOI: 10.1016/j.urology.2006.10.041. View

10.

Boyland E, Williams D . The metabolism of tryptophan. 2. The metabolism of tryptophan in patients suffering from cancer of the bladder. Biochem J. 1956; 64(3):578-82. PMC: 1199777. DOI: 10.1042/bj0640578. View

11.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

12.

Ritterson Lew C, Guin S, Theodorescu D . Targeting glycogen metabolism in bladder cancer. Nat Rev Urol. 2015; 12(7):383-91. PMC: 4678000. DOI: 10.1038/nrurol.2015.111. View

13.

McCarthy D, Chen Y, Smyth G . Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 2012; 40(10):4288-97. PMC: 3378882. DOI: 10.1093/nar/gks042. View

14.

Donin N, Lenis A, Holden S, Drakaki A, Pantuck A, Belldegrun A . Immunotherapy for the Treatment of Urothelial Carcinoma. J Urol. 2016; 197(1):14-22. DOI: 10.1016/j.juro.2016.02.3005. View

15.

Hansen M, Cavenee W . Retinoblastoma and the progression of tumor genetics. Trends Genet. 1988; 4(5):125-8. DOI: 10.1016/0168-9525(88)90134-5. View

16.

Margueron R, Reinberg D . The Polycomb complex PRC2 and its mark in life. Nature. 2011; 469(7330):343-9. PMC: 3760771. DOI: 10.1038/nature09784. View

17.

Yang W, Soares J, Greninger P, Edelman E, Lightfoot H, Forbes S . Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2012; 41(Database issue):D955-61. PMC: 3531057. DOI: 10.1093/nar/gks1111. View

18.

Siegel R, Miller K, Jemal A . Cancer statistics, 2016. CA Cancer J Clin. 2016; 66(1):7-30. DOI: 10.3322/caac.21332. View

19.

Plimack E, Dunbrack R, Brennan T, Andrake M, Zhou Y, Serebriiskii I . Defects in DNA Repair Genes Predict Response to Neoadjuvant Cisplatin-based Chemotherapy in Muscle-invasive Bladder Cancer. Eur Urol. 2015; 68(6):959-67. PMC: 4764095. DOI: 10.1016/j.eururo.2015.07.009. View

20.

OLeary B, Finn R, Turner N . Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol. 2016; 13(7):417-30. DOI: 10.1038/nrclinonc.2016.26. View