ZW10 interacting kinetochore protein may serve as a prognostic biomarker for human breast cancer: An integrated bioinformatics analysis

Abstract

ZW10 interacting kinetochore protein (ZWINT) is an essential component for the mitotic spindle checkpoint and has been reported to be upregulated in numerous types of human cancer. Nonetheless, its role in breast cancer (BC) remains unclear. Herein, it was demonstrated that the expression of ZWINT was significantly higher in BC than in normal breast tissues, on the basis of integrated analysis of bioinformatics studies, cancer database analyses and immunohistochemical detection. Elevated ZWINT levels were associated with a number of clinicopathological characteristics in patients with BC. These characteristics include: i) Positive human epidermal growth factor receptor 2 expression; ii) triple-negative BC; iii) younger age; iv) basal-like subtype; and v) greater Scarff-Bloom-Richardson grades. Additionally, prognostic analysis indicated that shorter relapse-free survival, overall survival and metastatic relapse-free survival may be associated with high ZWINT expression. A total of 16 pathways associated with high ZWINT expression, including Myc targets V1/2, DNA repair and mitotic spindle pathways, were identified using Gene Set Enrichment Analysis. In addition, a positive correlation between cyclin-dependent kinase 1 (CDK1) and ZWINT mRNA expression was identified by co-expression analysis. The present study suggested that ZWINT may serve as an effective prognostic biomarker for BC. In addition, ZWINT may be implicated in the CDK1-mediated initiation and progression of BC. However, further research is required to understand the role of ZWINT in BC.

Construction of Prognostic Risk Prediction Model of Oral Squamous Cell Carcinoma Based on Nine Survival-Associated Metabolic Genes

“…In order to understand the expression pathways of these key genes, these key genes were defined as a set of genes for GSEA, which is a computational tool commonly employed to interpret gene expression data by evaluating whether a pre-defined set of genes demonstrates statistically significant ( Subramanian et al, 2005 ; Li et al, 2020 ). The terms with P -value < 0.05 obtained in GSEA was considered significant and the top 10 terms were visualized using “ggplot2” package.…”

To Ubiquitinate or Not to Ubiquitinate: TRIM17 in Cell Life and Death

“…TRIM17 is also involved in mitosis by inducing the degradation of key components of the mitotic spindle machinery, midbodies and the kinetochore protein ZWINT, via autophagy and UPS, respectively [ 68 , 73 ]. Notably, ZWINT is upregulated in many human cancers and is associated with poor clinical prognosis and early recurrence [ 145 , 146 ]. Conversely, ZWINT knockdown effectively inhibits proliferation of glioblastoma cells in vitro and suppresses glioblastoma growth in vivo [ 146 ].…”

Zwint facilitates melanoma progression by promoting c‑Myc expression

“…For instance, Zwint expression was indicated to be associated with the expression levels of PCNA, Cdc25C, cyclin B1 and CDK1( 11 ). Li et al ( 10 ) reported that high Zwint expression was closely associated with cell cycle-related molecules and pathways, such as Myc targets V1/2, DNA repair, mitotic spindle, G2M checkpoint and E2F targets. In addition, Peng et al ( 13 ) demonstrated that Zwint knockdown affected the expression of molecules associated with TNF signaling and other pathways.…”

“…Therefore, it may be hypothesized that an abnormal expression or structure of Zwint may be associated with carcinogenesis. Previous studies have reported that Zwint is overexpressed in various types of tumors and is associated with a poor prognosis ( 10-12 ). In addition, it has been demonstrated that Zwint may act as an oncogene ( 11 , 13 ).…”