Abstract
To identify novel genes in castration-resistant prostate cancer (CRPC), we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus (GEO). R packages affy and limma were performed to identify differentially expressed genes (DEGs) between primary prostate cancer and CRPC. After that, we performed functional enrichment analysis including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. In addition, protein-protein interaction (PPI) analysis was used to search for hub genes. Finally, to validate the significance of these genes, we performed survival analysis. As a result, we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets. Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosterone-regulated sodium reabsorption pathway. PPI network identified hub genes like cortactin-binding protein 2 (CTTNBP2), Rho family guanosine triphosphatase (GTPase) 3 (RND3), protein tyrosine phosphatase receptor-type R (PTPRR), Jagged1 (JAG1), and lumican (LUM). Based on PPI network analysis and functional enrichment analysis, we identified two genes (PTPRR and JAG1) as key genes. Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer. In conclusion, PTPRR and JAG1 are key genes in the CRPC, which may serve as promising biomarkers of diagnosis and prognosis of CRPC.
摘要
目的
鉴定去势抵抗性前列腺癌(CRPC)的关键基因.
创新点
(1)结合多个数据库数据,运用生物信息学方 法鉴定CRPC 的关键基因; (2)首次报道PTPRR 可能在CRPC 里起关键作用.
方法
通过下载三个GEO 数据库的mRNA 微阵列数据, 分析CRPC 和激素敏感前列腺癌之间的基因差 异,对筛选出的差异基因进行功能富集分析和蛋 白质间相互作用分析,最终筛选出两个有重要功 能的差异基因(PTPRR 和JAG1).通过在多个 其他数据库中进行表达量验证和生存分析,进一 步证明这些基因的重要作用.
结论
PTPRR 和JAG1 在CRPC 中显著增高,并与预后 差相关.因此,这两个基因有可能作为CRPC 的 诊断和预后的生物标志物.
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Acknowledgments
The authors would like to thank The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) programs for providing high quality data.
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Contributions
Guo-ping REN and Ji-li WANG conceived and designed the study. Ji-li WANG and Yan WANG collected the data and analyzed the data. Ji-li WANG wrote the original draft. Guo-ping REN and Yan WANG reviewed and edited the manuscript. All authors have read and approved the final manuscript. All authors have full access to all the data in the study and have responsibility for the integrity and security of the data.
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Table S1 Clinical characteristics of samples in this study Fig. S1 Expression of the PTPRR in Grasso PCa
Data availability
The data that support the findings of this study are openly available in Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo), and the code for analysis in this article can be obtained by emailing the corresponding author.
Compliance with ethics guidelines
Ji-li WANG, Yan WANG, and Guo-ping REN declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods
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Wang, Jl., Wang, Y. & Ren, Gp. Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods. J. Zhejiang Univ. Sci. B 21, 246–255 (2020). https://doi.org/10.1631/jzus.B1900329
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DOI: https://doi.org/10.1631/jzus.B1900329
Key words
- Bioinformatics
- Protein tyrosine phosphatase receptor-type R (PTPRR)
- Jagged1 (JAG1)
- Differentially expressed genes (DEGs)
- Castration-resistant prostate cancer (CRPC)
- Functional enrichment