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Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer
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 ex...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797459/ https://www.ncbi.nlm.nih.gov/pubmed/35116546 http://dx.doi.org/10.21037/tcr-20-3166 |
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author | Fan, Jun Zhang, Zhe Chen, Dongjiao Chen, Hongqiang Yuan, Wenbo Zhou, Lu Xu, Jing Liu, Wenbin Xu, Yan |
author_facet | Fan, Jun Zhang, Zhe Chen, Dongjiao Chen, Hongqiang Yuan, Wenbo Zhou, Lu Xu, Jing Liu, Wenbin Xu, Yan |
author_sort | Fan, Jun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8797459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-87974592022-02-02 Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer Fan, Jun Zhang, Zhe Chen, Dongjiao Chen, Hongqiang Yuan, Wenbo Zhou, Lu Xu, Jing Liu, Wenbin Xu, Yan Transl Cancer Res Original Article 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. AME Publishing Company 2021-05 /pmc/articles/PMC8797459/ /pubmed/35116546 http://dx.doi.org/10.21037/tcr-20-3166 Text en 2021 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/. |
spellingShingle | Original Article Fan, Jun Zhang, Zhe Chen, Dongjiao Chen, Hongqiang Yuan, Wenbo Zhou, Lu Xu, Jing Liu, Wenbin Xu, Yan Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer |
title | Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer |
title_full | Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer |
title_fullStr | Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer |
title_full_unstemmed | Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer |
title_short | Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer |
title_sort | bioinformatic analysis of the expression and prognosis of znf589 in human breast cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797459/ https://www.ncbi.nlm.nih.gov/pubmed/35116546 http://dx.doi.org/10.21037/tcr-20-3166 |
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