BUB1B 过表达是肾细胞癌的一个独立预后标志物，并与 CD44、p53 和 PD-L1 相关。
BUB1B Overexpression Is an Independent Prognostic Marker and Associated with CD44, p53, and PD-L1 in Renal Cell Carcinoma.
机构信息
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan,
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
出版信息
Oncology. 2021;99(4):240-250. doi: 10.1159/000512446. Epub 2021 Feb 15.
INTRODUCTION
BUB1 mitotic checkpoint serine/threonine kinase B encoded by BUB1B gene is a member of the spindle assembly checkpoint family. Several reports have demonstrated that overexpression of BUB1B is associated with cancer progression and prognosis.
OBJECTIVE
This study aims to clarify the expression and function of BUB1B in renal cell carcinoma (RCC).
METHODS
The expression of BUB1B was determined using immunohistochemistry and bioinformatics analysis in RCC. The effects of BUB1B knockdown on cell growth and invasion were evaluated. We analyzed the interaction between BUB1B, cancer stem cell markers, p53, and PD-L1 in RCC.
RESULTS
In 121 cases of RCC, immunohistochemistry showed that 30 (25%) of the RCC cases were positive for BUB1B. High BUB1B expression was significantly correlated with high nuclear grade, T stage, and M stage. A Kaplan-Meier analysis showed that the high expression of BUB1B was associated with poor overall survival after nephrectomy. High BUB1B expression was associated with CD44, p53, and PD-L1 in RCC. Knockdown of BUB1B suppressed cell growth and invasion in RCC cell lines. Knockdown of BUB1B also suppressed the expression of CD44 and increased the expression of phospho-p53 (Ser15). In silico analysis showed that BUB1B was associated with inflamed CD8+, exhausted T-cell signature, IFN-γ signature, and the response to nivolumab.
CONCLUSION
These results suggest that BUB1B plays an oncogenic role and may be a promising predictive biomarker for survival in RCC.
简介
BUB1 有丝分裂检查点丝氨酸/苏氨酸激酶 B 由 BUB1B 基因编码，是纺锤体组装检查点家族的成员。有几项报告表明，BUB1B 的过表达与癌症的进展和预后有关。
目的
本研究旨在阐明 BUB1B 在肾细胞癌（RCC）中的表达和功能。
方法
采用免疫组织化学和生物信息学分析方法检测 RCC 中 BUB1B 的表达。评估 BUB1B 敲低对细胞生长和侵袭的影响。我们分析了 BUB1B 与癌症干细胞标志物、p53 和 PD-L1 在 RCC 中的相互作用。
结果
在 121 例 RCC 中，免疫组织化学显示 30 例（25%）RCC 病例 BUB1B 阳性。高 BUB1B 表达与核分级高、T 分期和 M 分期显著相关。Kaplan-Meier 分析显示，BUB1B 高表达与肾切除术后总生存期不良相关。BUB1B 在 RCC 中的表达与 CD44、p53 和 PD-L1 相关。BUB1B 敲低抑制 RCC 细胞系的细胞生长和侵袭。BUB1B 敲低还抑制 CD44 的表达，增加磷酸化 p53（Ser15）的表达。计算机分析显示 BUB1B 与炎症性 CD8+、耗竭性 T 细胞特征、IFN-γ 特征和对 nivolumab 的反应相关。
结论
这些结果表明 BUB1B 发挥致癌作用，可能是 RCC 患者生存的有前途的预测生物标志物。
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