Department of Urology, University of Tuebingen Hospital, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
Department of Urology, Center for Medical Research, University of Tuebingen Hospital, Waldhoernlestrasse 22, 72072, Tübingen, Germany.
BMC Urol. 2021 Apr 12;21(1):60. doi: 10.1186/s12894-021-00829-0.
CD276 is an immune checkpoint molecule. Elevated CD276 expression by urothelial carcinoma is associated with poor prognosis, but little is known about its expression across different tumor stages. We therefore investigated CD276 expression in bladder cancer (BC) cells and in tissue samples of BC stages from pT2 to pT4.
CD276 expression was explored in 4 urothelial cancer cell lines and 4 primary normal urothelial cell populations by quantitative RT-PCR, Western blot and flow cytometry. CD276 was investigated in bladder tumors from 98 patients by immunohistochemistry using a score (0-300) incorporating both, staining intensity and area of CD276 staining. Normal appearing urothelium in the bladder of the same patients served as controls.
The urothelial carcinoma cell lines expressed significantly higher levels of CD276 on transcript (p < 0.006), total protein levels (p < 0.005), and on the cell surface (p < 0.02) when compared to normal urothelial cells. In pT2-T4 tumor tissue samples, CD276 was overexpressed (median score 185) when compared to corresponding healthy tissues from the same patients (median score 50; p < 0.001). No significant differences in CD276 expression were recorded in late, locally advanced ≥ pT3a tumors (median score 185) versus organ-confined < pT3a tumors (median score 190), but it was significantly lower in the normal urothelial tissue associated with ≥ pT3a tumors (median score 40) versus < pT3a tumors (median score 80; p < 0.05).
CD276 expression is significantly elevated in urothelial carcinoma cells in all stages but varies between individuals considerably. Reduced CD276 expression in normal urothelial cells may imply that these cells would be protected from CD276-mediated immuno therapies.
CD276 是一种免疫检查点分子。膀胱癌中 CD276 的表达升高与预后不良相关，但对于其在不同肿瘤分期中的表达情况知之甚少。因此，我们研究了 CD276 在膀胱癌（BC）细胞中的表达，并在 pT2 至 pT4 不同肿瘤分期的 BC 组织样本中进行了检测。
通过定量 RT-PCR、Western blot 和流式细胞术检测 4 种尿路上皮癌细胞系和 4 种原发性正常尿路上皮细胞群体中 CD276 的表达。使用包含 CD276 染色强度和面积的评分（0-300），通过免疫组织化学方法检测 98 例膀胱癌患者的膀胱癌肿瘤中 CD276 的表达情况，同时使用同一患者膀胱中的正常外观尿路上皮作为对照。
与正常尿路上皮细胞相比，尿路上皮癌细胞系在转录本（p<0.006）、总蛋白水平（p<0.005）和细胞表面（p<0.02）上表达的 CD276 水平明显更高。与同一患者的相应健康组织相比，pT2-T4 肿瘤组织样本中 CD276 表达过度（中位数评分 185）（p<0.001）。在局部晚期≥pT3a 肿瘤（中位数评分 185）与器官局限的<pT3a 肿瘤（中位数评分 190）之间，CD276 的表达无显著差异，但与<pT3a 肿瘤相比，与≥pT3a 肿瘤相关的正常尿路上皮组织中的 CD276 表达明显较低（中位数评分 40）（p<0.05）。
CD276 在所有分期的尿路上皮癌细胞中表达均显著升高，但个体间差异较大。正常尿路上皮细胞中 CD276 表达减少可能意味着这些细胞将免受 CD276 介导的免疫治疗的影响。
