Abstract 202: Identification of survival associated hub genes in prostate cancer patients from the TCGA database

N. Reyes, R. Tiwari, J. Geliebter
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Abstract

Background: Prostate cancer is the most frequently diagnosed malignancy and the fourth leading cause of cancer-related death in the global male population. Although the disease has a relatively low mortality rate with some patients surviving for 10-20 years after treatment, others respond poorly to treatment and die of metastatic disease within 2-3 years. Therefore, there is an urgent need to develop strategies to identify patients with clinically significant prostate cancer requiring aggressive treatment to improve survival, while sparing others unnecessary side effects. The purpose of this study was to identify survival associated genes in prostate cancer patients from the TCGA database using bioinformatics tools. Methods: Data from prostate cancer patients in the TCGA database were divided into two study groups: a high and a low expression group, relative to the median expression. The Gene Expression Profiling Interactive Analysis (GEPIA2) tool was used for the identification of the most differential survival genes. Metascape bioinformatics tool was subsequently used for clustering of genes based on processes, pathway enrichment analysis, and construction of Protein-Protein Interaction (PPI) network. Metascape was also used for molecular Complex Detection (MCODE) to identify the genes with the highest degree of connection, known as hub genes, and to screen modules of the PPI network. Results: Bioinformatics analysis allowed the identification of 361 genes whose expression levels were significantly associated with overall survival in prostate cancer patients from the TCGA. Survival associated genes were primarily enriched in mRNA processing, DNA repair, ncRNA processing, DNA replication, macromolecule methylation, among others. The 12 most connected genes were selected as hub genes and Kaplan-Meier analysis was used to verify survival associated with this set of genes. Hub genes included several splicing factors and components of the processing machinery of cellular pre-mRNAs. Conclusions: These hub genes may reveal basic mechanisms underlying the development of clinically relevant prostate cancer and contribute to the identification of novel markers for prognosis of this cancer. Citation Format: Niradiz Reyes, Raj Tiwari, Jan Geliebter. Identification of survival associated hub genes in prostate cancer patients from the TCGA database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 202.
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202: TCGA数据库中前列腺癌患者生存相关枢纽基因的鉴定
背景:前列腺癌是全球男性人群中最常见的恶性肿瘤,也是癌症相关死亡的第四大原因。虽然这种疾病的死亡率相对较低,一些患者在治疗后存活10-20年,但其他患者对治疗反应不佳,在2-3年内死于转移性疾病。因此,迫切需要制定策略来识别需要积极治疗的临床显著前列腺癌患者,以提高生存率,同时避免其他不必要的副作用。本研究的目的是利用生物信息学工具从TCGA数据库中识别前列腺癌患者的生存相关基因。方法:将TCGA数据库中前列腺癌患者的数据,相对于中位表达分为高表达组和低表达组两组。基因表达谱交互分析(GEPIA2)工具用于鉴定大多数差异生存基因。随后使用Metascape生物信息学工具进行基于过程的基因聚类、途径富集分析和蛋白质-蛋白质相互作用(PPI)网络的构建。metscape还用于分子复合物检测(MCODE),以鉴定连接程度最高的基因,称为枢纽基因,并筛选PPI网络的模块。结果:生物信息学分析鉴定出361个基因,这些基因的表达水平与TCGA中前列腺癌患者的总生存率显著相关。生存相关基因主要富集于mRNA加工、DNA修复、ncRNA加工、DNA复制、大分子甲基化等。选取关联性最大的12个基因作为枢纽基因,采用Kaplan-Meier分析验证该组基因的相关生存率。枢纽基因包括几个剪接因子和细胞前mrna加工机制的组成部分。结论:这些中心基因可能揭示了临床相关前列腺癌发生的基本机制,并有助于发现前列腺癌预后的新标志物。引文格式:Niradiz Reyes, Raj Tiwari, Jan Geliebter。TCGA数据库中前列腺癌患者生存相关枢纽基因的鉴定[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要第202期。
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