Identification of biomarkers, pathways and potential therapeutic target for docetaxel resistant prostate cancer

ABSTRACT

Docetaxel has been proved to provide survival benefit for advanced prostate cancer (PCa) patients. Resistance to docetaxel further reduces the survival of these patients. Herein, we performed a comprehensive bioinformatic analysis to identify differentially expressed genes (DEGs) between docetaxel sensitive and resistant PCa (DRPC) cell based on Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied for functional and pathway analysis of DEGs. The STRING database, cytoscape software and plug-in ‘cytoHubba’ were used to construct protein–protein interaction (PPI) networks and identify hub genes. Survival analysis were performed via GEPIA database. Finally, we conducted immune infiltration analysis by TIMER. A total of 460 DEGs were identified. GO functional analysis showed that these DEGs are mainly enriched in chemotaxis, negative regulation of intracellular signal transduction, and regulation of cell adhesion, positive regulation of inflammatory response, regulation of response to cytokine stimulus. According to the results of KEGG pathway analysis, these DEGs are mainly involved in signaling by Rho GTPases, Miro GTPases and RHOBTB3; interferon Signaling; arginine biosynthesis; PI3K-Akt signaling pathway; cytokine-cytokine receptor interaction; MAPK signaling pathway. Finally, CCNB1 and EZH2 were identified as prognostic hub genes and the expression of these two genes were associated with immune infiltration. The present study may helps to improve the understanding of the molecular mechanisms of DRPC and facilitate the selection of therapeutic and prognostic biomarkers for DRPC.

KEYWORDS:

• CRPC
• docetaxel resistance
• prognosis
• GEO

Highlights

1. CCNB1 and EZH2 were found to be hub genes in docetaxel-resistance PCa.

2. The expression of CCNB1 and EZH2 are associated with DFS in PCa patients.

(3) The expression of CCNB1 and EZH2 are positively related with multiple immune cells infiltration level.

Acknowlegements

We thank all the study authors for the support in this study.

Author contributions

RJL and SYL contributed equally to this manuscript. Study design, data extraction and analysis: RJL and SYL. Manuscript writing: RJL, SYL, LQL and BX. Manuscript reviewed and revised: RJL, BX and MC.

Ethics approval

This article is based on public data. Therefore, ethics and informed consent of patients are not involved.

Disclosure

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was funded by The National Natural Science Foundation of China (No. 81872089, 81370849, 81672551, 81300472, 81070592, 81202268, 81202034); Six talent peaks project in Jiangsu Province, Jiangsu Provincial Medical Innovation Team (CXTDA2017025); Natural Science Foundation of Jiangsu Province (BK20161434, BL2013032, BK20150642 and BK2012336);National Natural science foundation of Chnia [No. 81872089].