去势抵抗性前列腺癌神经内分泌转化的关键基因的研究

Key genes of castration resistance to neuroendocrine transformation in castrated resistant prostate cancer

目的通过生物信息学方法研究去势抵抗性前列腺癌发展成为神经内分泌性前列腺癌的关键基因。方法从cBioPortal数据库下载前列腺癌的转录本测序数据,使用R语言和加权基因共表达网络分析(WGCNA)软件包进行数据分析,明确癌症类型相关性最高的基因集。对该基因集进行基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)分析,明确该群基因和细胞周期及细胞分裂的相关性。再利用STRING数据库计算该基因集内基因的相关性,导入Cytoscape软件中构建基因网络,并计算出处于网络核心的前10个基因。然后在GSE105416数据集中验证这10个基因的表达。最后选择关键基因UBE2C和NUF2做GSEA分析。结果鉴定了10个在前列腺癌神经内分泌转化中的关键基因,分别是BUB1、CDCA8、CEN-PF、HJURP、KIF23、KIF2C、NUF2、PTTG1、TPX2和UBE2C。结论本研究对前列腺癌的神经内分泌转化提供了新视角,鉴定出关键基因可作用于影响前列腺癌细胞的细胞周期和AR信号通路来影响其神经内分泌转化。

Objective We used bioinformatic methods to explore hub genes involved in the development of castrationresistant prostate cancer(CRPC)into neuroendocrine prostate cancer(NEPC).Methods Data from the cBioPortal database were downloaded.We used the WGCNA package in the R language and identified the turquoise gene module which having the strongest relationship with the group data.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis suggested that the turquoise gene module had a strong interaction with the cell cycle and cell division.We also used the STRING database to calculate the combined correlation coefficient for the identified genes and submitted that information to Cytoscape to structure the network of the top 10 genes.Then,we identified the expression profiles of the top 10 genes in the data from GSE105416 and found that they were analogous to the expression profiles in the tissue samples.Finally,we chose the UBE2C gene and the NUF2 for gene set enrichment analysis.Results We identified 10 hub genes involved in the development of CRPC into NEPC.There genes were BUB1,CDCA8,CENPF,HJURP,KIF23,KIF2C,NUF2,PTTG1,TPX2 and UBE2C.Conclusions Our findings provide several new insights for the identification of key genes involved in the transformation of CRPC into NEPC.These genes might impact the cell cycle and cell division and should be studied further.