Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Department of Pathology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Yonsei Med J. 2021 Aug;62(8):679-690. doi: 10.3349/ymj.2021.62.8.679.
Eph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles of EphB receptors (EphB2, B3, and B4) in urinary bladder cancer.
Tissue microarray-based immunohistochemical analysis was used to investigate the expression patterns of EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining the extent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was more than moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression in bladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration.
EphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4, 82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumor grade (EphB2, <0.001; EphB3, =0.032; EphB4, <0.001) and muscular invasion (EphB2, =0.002; EphB3, =0.009; EphB4, <0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph node involvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumor cell invasion, proliferation, and migration in comparison with untransfected cancer cells.
Low expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.
Eph 受体在多种恶性肿瘤中呈现差异表达。本研究旨在分析 EphB 受体（EphB2、B3 和 B4）在膀胱癌中的作用。
采用组织微阵列免疫组织化学分析方法，检测 EphB2、B3 和 B4 在 154 例膀胱癌标本中的表达模式。免疫组化染色检测染色细胞的范围和染色强度。当组织切片中 >25%的细胞染色强度超过中度时，认为 EphB 表达较高。使用小干扰 RNA（siRNA）敲低膀胱癌细胞系（T24、5637）中的 EphB 表达，以确定 EphB 对肿瘤细胞侵袭、增殖和迁移的影响。
EphB 受体（B2、B3 和 B4）在 40.9%（EphB2，63/154）、71.4%（EphB3，110/154）和 53.2%（EphB4，82/154）的膀胱癌标本中检测到。EphB2、B3 和 B4 受体的低表达与肿瘤分级较高（EphB2，<0.001；EphB3，=0.032；EphB4，<0.001）和肌肉浸润（EphB2，=0.002；EphB3，=0.009；EphB4，<0.001）显著相关。与其他临床病理变量（如年龄、性别、复发、淋巴结受累、转移和总生存期）无明显相关性。与未转染的癌细胞相比，EphB 受体的 siRNA 转染失活增加了细胞活力、肿瘤细胞侵袭、增殖和迁移。
EphB 受体（B2、B3 和 B4）的低表达可能是膀胱癌肌肉浸润的预测标志物。
