Protein Expression of Programmed Death 1 Ligand 1 and HER2 in Gastric Carcinoma
Protein Expression of Programmed Death 1 Ligand 1 and HER2 in Gastric Carcinoma
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DOI：
10.1159/000479231
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发表时间：
2017-01-01
期刊：
影响因子：
3.5
通讯作者：
Maehara, Yoshihiko
中科院分区：
文献类型：
--
作者：
Oki, Eiji;Okano, Shinji;Maehara, Yoshihiko
目的：程序性死亡1（PD-1）是一种免疫抑制受体，已被确定为癌症免疫治疗的新靶点。在这里，我们报告了手术切除的胃癌中 PD-1 配体 1 (PD-L1) 的表达。材料和方法：我们检查了 144 名初步诊断为胃癌的胃癌患者的福尔马林固定肿瘤样本。采用免疫组织化学方法检测PD-L1。在这些患者中研究了人表皮生长因子受体 2 (HER2) 表达以及磷酸酶和张力蛋白同源物 (PTEN) 杂合性丢失。 RNA干扰用于下调HER2表达，并使用胃癌细胞系MKN45通过流式细胞术评估PD-L1蛋白表达。结果：PD-L1 过度表达与肿瘤侵袭显着相关 (p = 0.011)，并与较差的生存率相关。 PD-L1阳性病例数根据临床样本中的HER2评分而增加。 siRNA 介导的 HER2 下调显着降低了 MKN45 细胞中 PD-L1 蛋白的表达。结论：PD-L1表达与胃癌不良生存相关，HER2信号传导影响胃癌中PD-L1的表达。在胃癌中，PTEN 和 HER2 是开发阻断 PD-L1 的人类抗体的潜在候选生物标志物。 (c) 2017 S. Karger AG，巴塞尔
Objectives: Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer. Materials and Methods: We examined formalin-fixed tumor samples from 144 gastric cancer patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients. RNA interference was used to downregulate HER2 expression, and PD-L1 protein expression was assessed by flow cytometry using the gastric cancer cell line MKN45. Results: Overexpression of PD-L1 was significantly correlated with tumor invasion (p = 0.011) and associated with poor survival. The number of PD-L1-positive cases increased according to the HER2 score in clinical samples. siRNA-mediated downregulation of HER2 significantly decreased PD-L1 protein expression in MKN45 cells. Conclusions: PD-L1 expression was associated with poor survival of gastric cancer, and HER2 signaling affects the expression of PD-L1 in gastric cancer. In gastric cancer, PTEN and HER2 are potential candidate biomarkers for developing human antibodies that block PD-L1. (c) 2017 S. Karger AG, Basel