Prognostic values of spindle checkpoint protein BUB1B in triple negative breast cancer
10.3760/cma.j.cn112151-20210131-00108
- VernacularTitle:纺锤体检测点蛋白BUB1B在三阴型乳腺癌中的表达及意义
- Author:
Peichuan ZHANG
1
;
Xiaorong ZHONG
;
Hong ZHENG
;
Li LI
;
Fei CHEN
;
Mengjia SHEN
;
Yijie LI
;
Hong CHEN
;
Shiyu CAO
;
Hong BU
;
Feng YE
Author Information
1. 四川大学华西医院卫健委移植工程与移植免疫重点实验室 临床病理研究所，成都610041
- Keywords:
Breast neoplasms;
Biological markers;
Prognosis
- From:
Chinese Journal of Pathology
2021;50(6):645-649
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To identify important prognostic molecular markers of triple negative breast cancer (TNBC) using high throughput sequencing technology and to explore the correlation of spindle checkpoint protein BUB1B and clinicopathological features with patients′ prognosis.Methods:The clinicopathological data and prognostic information of TNBC diagnosed at the West China Hospital of Sichuan University from 2009 to 2017 were collected. Forty-seven fresh tumor samples and 139 formalin fixed paraffin-embedded samples were selected. The fresh tumor samples were subject to RNA sequencing (RNA-seq). The enrichment analysis and protein-protein interaction (PPI) analysis were performed after intersection of difference analysis between RNAseq and GEO (Gene Expression Omnibus) datasets GSE38959 and GSE65194. Kaplan-Meier plotter database was used to analyze the relationship between expression of BUB1B and prognosis. Immunohistochemical staining was used to verify its expression in TNBC and correlation with clinicopathological features and prognosis.Results:Using edgeR to perform differential expression analysis between 47 TNBC tumor tissues and 12 normal tissues, 1 559 up-regulated genes and 1 376 down-regulated genes were identified, while only 131 differentially expressed genes were overlapping with those in GSE38959 and GSE65194. Enrichment analysis was mainly enriched in cell cycle, JAK-STAT signaling pathway and p53 signaling pathway. The top 10 genes ranked by degree of association were TOP2A, BUB1B, MKI67, PLK1, RRM2, PCNA, KPNA2, SMC4, PBK and IGF1. Kaplan-Meier plotter database analysis showed that the expression of BUB1B was significantly correlated with the prognosis of TNBC [overall survival, hazard ratio (HR)=0.52, 95% CI (0.35-0.77), P=0.001; distant metastasis-free, HR=0.72, 95% CI (0.52-0.98), P=0.038]. The immunohistochemical analyses of 139 formalin fixed paraffin-embedded samples showed that the low expression of BUB1B was correlated with poor prognosis in TNBC [HR=0.41, 95% CI (0.18-0.95), P=0.024]. Conclusions:The low expression of BUB1B protein is associated with poor prognosis in TNBC patients, and the molecular mechanism related with prognosis and potential therapeutic targets need to be further studied.
