Xue Chunyan, Zhu Dawei, Chen Lujun, Xu Yun, Xu Bin, Zhang Dachuan, Jiang Jingting
Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Jiangsu Engineering Research Center for Tumor Immunotherapy, the Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Transl Cancer Res. 2019 Feb;8(1):111-119. doi: 10.21037/tcr.2019.01.09.
In the present study, we aimed to investigate the expression and prognostic value of co-stimulatory molecules, programmed death ligand-1 (PD-L1) and PD-L2, in ovarian cancer (OC).
Immunohistochemical (IHC) staining was used to assess the expressions of PD-L1 and PD-L2 in 77 cases of OC, and 10 cases of benign ovarian cyst were employed as negative controls. Moreover, χ test was used to analyze the correlation between the PD-L1/PD-L2 expression and clinicopathological parameters. Kaplan-Meier method was used to compare the effects of PD-L1/PD-L2 expression level on the overall survival (OS) of OC patients.
PD-L1 and PD-L2 were mainly expressed on membrane and in cytoplasm of OC cells. The high-expression rate of PD-L1 and PD-L2 in OC tissues was 44.16% (34/77) and 22.08% (17/77), respectively. The expression of PD-L1 in OC cells was significantly correlated with FIGO stage (P=0.026), while its expression was not significantly correlated with other clinicopathological parameters. There was no significant correlation between PD-L2 and any clinicopathological parameters. Kaplan-Meier survival analysis showed that the OS of high PD-L1 expression group was significantly shorter compared with the low PD-L1 expression group (HR =2.689, 95% CI: 1.400-5.163). Patients with high PD-L2 expression also exhibited significantly shorter OS (HR =2.204, 95% CI: 1.037-4.682). Multivariable analysis displayed that high expression of PD-L1 (HR =2.275, 95% CI: 1.120-4.169), high expression of PD-L2 (HR =2.314, 95% CI: 1.136-4.714) and FIGO stage (HR =11.229, 95% CI: 1.373-91.865) were independent prognostic factors of OC. When negative expressions of both PD-L1 and PD-L2 were used as a combined prognostic factor, the OS was significantly prolonged (HR =3.396, 95% CI: 1.858-6.029). According to our previous studies, patients with negative PD-L1 expression and high T-bet TIL infiltration have higher OS than other patients. Patients with positive PD-L1 expression and low T-bet TIL infiltration exhibit the shortest OS. Collectively, our findings provided the basis for PD-1/PD-L1 or PD-1/PD-L2 blockade therapy for OC patients.
Co-stimulatory molecules, PD-L1 and PD-L2, were highly expressed in OC tissues, and their expression levels were correlated with FIGO stage, age and prognosis. These results suggested that PD-L1 and PD-L2 were involved in the occurrence and development of malignant OC, indicating their potential value in clinical diagnosis and prognosis of OC.
在本研究中，我们旨在探讨共刺激分子程序性死亡配体-1（PD-L1）和PD-L2在卵巢癌（OC）中的表达及预后价值。
采用免疫组织化学（IHC）染色评估77例OC患者中PD-L1和PD-L2的表达，以10例良性卵巢囊肿作为阴性对照。此外，采用χ检验分析PD-L1/PD-L2表达与临床病理参数之间的相关性。采用Kaplan-Meier法比较PD-L1/PD-L2表达水平对OC患者总生存期（OS）的影响。
PD-L1和PD-L2主要表达于OC细胞的细胞膜和细胞质中。OC组织中PD-L1和PD-L2的高表达率分别为44.16%（34/77）和22.08%（17/77）。OC细胞中PD-L1的表达与国际妇产科联盟（FIGO）分期显著相关（P=0.026），而其表达与其他临床病理参数无显著相关性。PD-L2与任何临床病理参数均无显著相关性。Kaplan-Meier生存分析显示，PD-L1高表达组的OS明显短于低表达组（风险比[HR]=2.689，95%置信区间[CI]：1.400-5.163）。PD-L2高表达患者的OS也明显缩短（HR=2.204，95%CI：1.037-4.682）。多变量分析显示，PD-L1高表达（HR=2.275，95%CI：1.120-4.169）、PD-L2高表达（HR=2.314，95%CI：1.136-4.714）和FIGO分期（HR=11.229，95%CI：1.373-91.865）是OC的独立预后因素。当将PD-L1和PD-L2的阴性表达作为联合预后因素时，OS显著延长（HR=3.396，95%CI：1.858-6.029）。根据我们之前的研究，PD-L1表达阴性且T-bet阳性肿瘤浸润淋巴细胞（TIL）浸润高的患者比其他患者的OS更高。PD-L1表达阳性且T-bet TIL浸润低的患者OS最短。总体而言，我们的研究结果为OC患者的PD-1/PD-L1或PD-1/PD-L2阻断治疗提供了依据。
共刺激分子PD-L1和PD-L2在OC组织中高表达，其表达水平与FIGO分期、年龄及预后相关。这些结果表明，PD-L1和PD-L2参与了恶性OC的发生发展，提示它们在OC临床诊断和预后评估中的潜在价值。
