Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer

Abstract

Background: Zinc finger protein 589 (ZNF589) is a member of the zinc finger protein (ZNF) family and plays an important role in the differentiation of haemopoietic system stem cells. However, its effects on tumorigenesis and progression have not yet been reported. The purpose of this study was to explore the prognosis and underlying mechanism of ZNF589 in breast cancer (BRCA) through a bioinformatic analysis. Methods: ZNF589 transcription levels in a TCGA BC cohort were analysed and then validated using Oncomine and UALCAN. The prognostic value of ZNF589 was determined based on the overall survival (OS) and relapse-free survival (RFS) based on The Cancer Genome Atlas (TCGA) cohort and Kaplan-Meier (K-M) database. LinkedOmics and STRING were carried out to explore the potential co-expressed genes and interactive proteins as well as corresponding enrichment analysis. A Gene Set Enrichment Analysis (GSEA) was performed between two gene matrices separated by the median cut-off value of ZNF589. The methylation levels of the ZNF589 promoter were analysed using UALCAN. Results: ZNF589 was downregulated in breast tumours, and lower expression was associated with poor OS (P=0.047) and RFS (P=0.0043) according to TCGA. A subgroup analysis showed that the downregulation of ZNF589 was significantly associated with poor OS in stage 3-4 patients (P=0.0249) and progesterone receptor (PR)-negative patients (P=0.0002). Consistently, lower ZNF589 predicted poor RFS in stage 3-4 patients (P=0.0090), hormone receptor-negative patients [oestrogen receptor (ER)-, P=0.0129; PR-, P=0.0130; human epidermal growth factor receptor 2 (HER2)-, P<0.0001] and triple-negative BRCA patients (P=0.0052). Univariate and multivariate Cox regressions indicated that ZNF589 could act as an independent prognostic biomarker for OS based on age and TNM stage. Functional enrichment analysis of co-expressed genes and a protein-protein interaction (PPI) network both suggested that ZNF589 expression was negatively correlated with cell cycle progression at the transcriptional and protein-interactive levels. Finally, we found that the downregulation of ZNF589 correlated with promoter hypermethylation, and the corresponding subgroup analysis presented similar results. Conclusions: Our study highlighted that ZNF589 could act as a potential prognostic biomarker and a tumour suppressor in BRCA. A functional enrichment analysis suggested that ZNF589 may participate in multiple cancer-related pathways, including the cell cycle. Epigenetic factor promoter methylation could contribute to the downregulation of ZNF589 expression. However, deeper research about its function and underlying mechanism in cancer progression is required.