Renyu Zhou, Minting Liu, Ming Li, Yulong Peng, Xiaotan Zhang
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引用次数: 0
Abstract
Background: Budding uninhibited by benzimidazole 1 (BUB1) is a highly conserved serine/threonine kinase, showing prominent importance for proper function during mitosis. However, little is known about BUB1 mRNA expression in breast cancer (BRCA) and its correlation with prognosis and immune infiltration. Hence, we aimed to unveil its potential as groundbreaking biomarkers for immunotherapy efficacy and the prognosis of BRCA.
Methods: Database for Annotation, Visualization, and Integrated Discovery (DAVID) is a potent tool for identifying significant clusters of genes and pathways in the resulting dataset. In this study, gene set enrichment analysis of BUB1 was conducted using DAVID. The clinical characteristics of patients with or without altered BUB1 mRNA expression were compared using cBioPortal. Tumor Immune Estimation Resource (TIMER) is a known as database for comprehensive analysis of tumor-infiltrating immune cells in various cancers. In the present study, the relationship between BUB1 expression and the abundance of immune infiltrates was explored using TIMER in BRCA. Immunohistochemistry staining was performed to analyze the protein expression of BUB1 in tumor tissue specimens. We used PrognoScan and Kaplan-Meier Plotter to evaluate the prognosis of patients with different BUB1 expression levels.
Results: The expression of BUB1 in various tumor tissues was higher than that in adjacent normal tissues. BUB1 was mainly localized to the nucleoplasm and additionally localized to the cytosol. Functional enrichment analyses revealed that the cell cycle was the most significant pathway. Abnormal BUB1 mRNA expression was more frequently detected in invasive ductal carcinoma with higher histological grades and BRCAs with estrogen receptor (ER)-negative, human epidermal growth receptor 2 (HER2)-negative, and basal-like phenotypes. The BUB1 expression was correlated positively with tumor purity, B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells, while BUB1 had no significant correlation with macrophages. The results of immunohistochemical staining from clinical samples further confirmed that BUB1 was overexpressed in BRCA compared to benign tumor (fibroadenoma of breast) (P<0.01). BRCA patients with lower BUB1 expression had a better prognosis than those with higher BUB1 expression in overall survival (OS) curves, distant metastasis-free survival (DMFS) curves, and relapse-free survival (RFS) curves (P<0.05).
Conclusions: Our results suggest that BUB1 is a potential molecular biomarker for evaluating the prognosis and predicting the effectiveness of immunotherapy for BRCA.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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