Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Graduate School of Medicine, Mie University, Mie, Japan.
Ann Surg Oncol. 2019 Mar;26(3):876-883. doi: 10.1245/s10434-018-07112-x. Epub 2018 Dec 18.
This study assessed programmed cell death ligand 1 (PD-L1) expression in primary tissues and soluble PD-L1 (sPD-L1) concentration in matched preoperative serum in gastric cancer (GC) patients to perform direct comparison between tissue and serum PD-L1 expression and to clarify the prognostic implication in GC.
The study enrolled 180 GC patients who underwent surgery for GC at the authors' institution. The study evaluated tissue PD-L1 expression using immunohistochemistry and quantified sPD-L1 concentration in preoperative serum using enzyme-linked immunosorbent assay in GC patients.
The findings showed that PD-L1 was overexpressed in GC tissues compared with normal mucosa. Tissue PD-L1 expression was significantly higher in the GC patients with advanced T stage, presence of lympho-vascular invasion, lymph node metastasis, and peritoneal metastasis. Furthermore, elevated tissue PD-L1 expression was significantly associated with poor prognosis for overall survival (OS) and disease-free survival (DFS). Serum sPD-L1 was significantly higher in the GC patients than in the healthy volunteers. Although serum sPD-L1 was not correlated with any clinicopathologic factors, the patients with high serum sPD-L1 showed poorer OS and DFS than those with low sPD-L1. Multivariate analyses showed that both elevated tissue PD-L1 and serum sPD-L1 were independent prognostic factors for poor OS [tissue PD-L1: hazard ratio (HR), 4.28; 95% confidence interval (CI), 1.43-12.8; P = 0.0094 vs. serum sPD-L1: HR, 11.2; 95% CI, 3.44-36.7; P = 0.0001] and poor DFS (tissue PD-L1: HR, 6.96; 95% CI, 2.48-19.6; P = 0.0002 vs. serum sPD-L1: HR, 8.7; 95% CI, 3.16-23.9; P < 0.0001) for the GC patients. Furthermore, infiltrative CD8- and Foxp3-positive T cells were significantly increased in the GC patients with elevated tissue PD-L1 expression.
Both serum sPD-L1 and tissue PD-L1 expression may serve as predictive biomarkers for recurrence and prognosis in GC patients.
本研究评估了原发性组织中程序性细胞死亡配体 1（PD-L1）的表达和胃癌（GC）患者术前血清中可溶性 PD-L1（sPD-L1）的浓度，以直接比较组织和血清 PD-L1 的表达，并阐明其在 GC 中的预后意义。
本研究纳入了 180 名在作者所在机构接受 GC 手术的 GC 患者。本研究使用免疫组织化学检测组织 PD-L1 的表达，并使用酶联免疫吸附试验检测 GC 患者术前血清中 sPD-L1 的浓度。
研究结果显示，GC 组织中 PD-L1 的表达高于正常黏膜。GC 患者中 T 分期较晚、存在淋巴血管侵犯、淋巴结转移和腹膜转移的患者组织 PD-L1 表达更高。此外，组织 PD-L1 表达升高与总生存期（OS）和无病生存期（DFS）的不良预后显著相关。GC 患者血清 sPD-L1 明显高于健康志愿者。尽管血清 sPD-L1 与任何临床病理因素均无相关性，但血清 sPD-L1 较高的患者 OS 和 DFS 较血清 sPD-L1 较低的患者差。多变量分析显示，升高的组织 PD-L1 和血清 sPD-L1 均是 OS 不良的独立预后因素[组织 PD-L1：危险比（HR），4.28；95%置信区间（CI），1.43-12.8；P=0.0094 vs. 血清 sPD-L1：HR，11.2；95%CI，3.44-36.7；P=0.0001]和 DFS 不良的独立预后因素（组织 PD-L1：HR，6.96；95%CI，2.48-19.6；P=0.0002 vs. 血清 sPD-L1：HR，8.7；95%CI，3.16-23.9；P<0.0001）。此外，在组织 PD-L1 表达升高的 GC 患者中，浸润性 CD8-和 Foxp3-阳性 T 细胞显著增加。
血清 sPD-L1 和组织 PD-L1 的表达均可作为 GC 患者复发和预后的预测生物标志物。
