Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Jpn J Clin Oncol. 2022 Apr 6;52(4):331-345. doi: 10.1093/jjco/hyab214.
Till now, no experiment has been performed to detect programmed death ligand 1 (PD-L1)/programmed death 1 (PD-1), soluble PD-L1/soluble PD-1 simultaneously in perioperative patients of gastric carcinoma. Our experiment aims at determining the clinical significance and possible mechanism of soluble PD-L1/soluble PD-1 in gastric carcinoma.
Thirty patients undergone gastrectomy were selected as the experimental group. Tissue's programmed death ligand 1 and peripheral programmed death 1 were detected using immunofluorescence and flow cytometry. Soluble PD-L1 and soluble PD-1 were detected using enzyme-linked immunosorbent assay.
First, preoperative programmed death 1 was higher than control group and decreased to normal post-operatively. Preoperatively ,elevated levels of programmed death 1 on cluster of differentiation (CD)4 T cells indicated less lymphatic metastasis (P < 0.01) and small tumor volume (P < 0.01); elevated programmed death 1 of CD8 T cells indicated big tumor volume (P < 0.01) and well histological differentiation (P < 0.01). Second, preoperative soluble PD-L1 and soluble PD-1 are lower than in control group. Post-operatively, the soluble PD-1 rose to normal, but the soluble PD-L1 showed no change. Third, programmed death ligand 1 can be observed in carcinoma tissue. Fourth, the area under the curve of soluble PD-1 (0.675) for diagnosis was worse than that of soluble PD-L1 (0.885). Kaplan-Meier analysis showed that soluble PD-1 < 245.26 pg/ml in post-operative serum predicted a poor prognosis (overall survival percentage: 60%) at 2 years (P < 0.05). Multivariate analysis revealed that carcinoembryonic antigen (>5 ng/l) and soluble PD-1 after gastrectomy (>245.26 pg/ml) were independent prognostic factors for overall survival (hazard ratio: 20.812, 95% confidence interval: 1.217-355.916, P = 0.036; hazard ratio: 0.028, 95% confidence interval: 0.001-0.786, P = 0.036, respectively).
We propose that soluble PD-1 combined with programmed death ligand 1 are effective not only in protecting T cells from the adhesion by programmed death ligand 1 but also in preventing the occurrence and the development of tumor as well. Through multivariate analysis, we found that soluble PD-1 was an independent protective factor for post-operative prognosis of gastric carcinoma patients, which indirectly verified the vital function of soluble PD-1. Soluble PD-1 might be promising predictive biomarkers for the diagnosis and prognosis of gastric carcinoma patients.
目前尚无实验同时检测胃癌围手术期患者程序性死亡配体 1（PD-L1）/程序性死亡 1（PD-1）和可溶性 PD-L1/可溶性 PD-1。本实验旨在探讨可溶性 PD-L1/可溶性 PD-1 在胃癌中的临床意义及可能的作用机制。
选择 30 例行胃癌根治术的患者作为实验组。采用免疫荧光和流式细胞术检测组织 PD-L1 和外周 PD-1，采用酶联免疫吸附试验检测可溶性 PD-L1 和可溶性 PD-1。
首先，术前 PD-1 高于对照组，术后降至正常。术前 CD4+T 细胞上 PD-1 水平升高提示淋巴转移较少（P<0.01）和肿瘤体积较小（P<0.01）；CD8+T 细胞上 PD-1 水平升高提示肿瘤体积较大（P<0.01）和组织学分化较好（P<0.01）。其次，术前可溶性 PD-L1 和可溶性 PD-1 均低于对照组。术后，可溶性 PD-1 恢复正常，但可溶性 PD-L1 无变化。第三，可在癌组织中观察到 PD-L1。第四，可溶性 PD-1 曲线下面积（0.675）的诊断效能低于可溶性 PD-L1（0.885）。Kaplan-Meier 分析显示，术后血清可溶性 PD-1<245.26 pg/ml 预测 2 年总生存率（60%）较差（P<0.05）。多因素分析显示，胃癌根治术后血清癌胚抗原（>5 ng/l）和可溶性 PD-1（>245.26 pg/ml）是总生存的独立预后因素（风险比：20.812，95%置信区间：1.217-355.916，P=0.036；风险比：0.028，95%置信区间：0.001-0.786，P=0.036）。
我们提出，可溶性 PD-1 与 PD-L1 结合不仅能有效保护 T 细胞免受 PD-L1 的黏附，还能预防肿瘤的发生和发展。通过多因素分析，我们发现可溶性 PD-1 是胃癌患者术后预后的独立保护因素，这间接验证了可溶性 PD-1 的重要功能。可溶性 PD-1 可能是胃癌患者诊断和预后的有前途的预测生物标志物。
