Oki Eiji, Okano Shinji, Saeki Hiroshi, Umemoto Yuichiro, Teraishi Koji, Nakaji Yu, Ando Koji, Zaitsu Yoko, Yamashita Nami, Sugiyama Masahiko, Nakashima Yuichiro, Ohgaki Kippei, Oda Yoshinao, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Oncology. 2017;93(6):387-394. doi: 10.1159/000479231. Epub 2017 Sep 15.
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.
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.
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.
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.
程序性死亡蛋白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。在此,我们报告了程序性死亡蛋白1配体1(PD-L1)在手术切除的胃癌中的表达情况。
我们检测了144例原发性胃癌患者经福尔马林固定的肿瘤样本。采用免疫组织化学法检测PD-L1。对这些患者研究了人表皮生长因子受体2(HER2)的表达及磷酸酶和张力蛋白同源物(PTEN)杂合性缺失情况。运用RNA干扰下调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。
PD-L1的过表达与肿瘤侵袭显著相关(p = 0.011),并与较差的生存率相关。临床样本中,PD-L1阳性病例数随HER2评分增加而增多。siRNA介导的HER2下调显著降低了MKN45细胞中PD-L1蛋白的表达。
PD-L1表达与胃癌患者较差的生存率相关,且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的人源抗体的潜在候选生物标志物。