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基于生物信息学分析的膀胱癌疾病进展及药物选择中突变的意义和机制分析

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

作者信息

Zhang Dingguo, Tian Jinjun, Xia Qier, Yang Zhenyu, Gu Bin

机构信息

Department of Urology, Shanghai Pudong New Area People's Hospital, Shanghai, China.

出版信息

Bladder Cancer. 2021 May 25;7(2):133-142. doi: 10.3233/BLC-200368. eCollection 2021.

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.

摘要

背景

膀胱癌仍然是一种具有显著发病率和死亡率的疾病。在膀胱癌中, 是最常见的突变基因之一。

方法

在本研究中,我们探索了癌症药物敏感性基因组学(GDSC)数据库中的药物敏感性。下载了最新的TCGA数据进行分析。为进行功能富集分析,使用了GSEA、KEGG和GO。使用GEPIA在线工具进行了预后分析。

结果

GDSC数据库的结果显示,具有 突变的膀胱癌细胞对达可替尼、MK-2206和GNE-317更具抗性。在25%的膀胱癌患者中发现了 突变。具有 突变的患者通常具有较低的 mRNA表达水平和较高的组织学分级。此外,我们在两组中鉴定出999个差异表达基因。功能富集分析表明,差异表达基因主要富集在多个代谢进程、细胞增殖和癌症相关途径中。WT1、GPR37、CHRM2和EZH2的表达水平与预后之间存在强相关性。

结论

总之,我们的结果表明了RB1突变在膀胱癌疾病进展和药物选择中的意义,并鉴定了与此程序相关的多个基因和途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb28/11181786/9e1403930fc4/blc-7-blc200368-g001.jpg

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