Gershtein E S, Ognerubov N A, Chang V L, Delektorskaya V V, Korotkova E A, Sokolov N Y, Polikarpova S B, Stilidi I S, Kushlinskii N E
N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia.
Medical Institute of G.R. Derzhavin Tambov State University of the Ministry of Science and Higher Education of the Russian Federation, Tambov, Russia.
Klin Lab Diagn. 2020;65(6):347-352. doi: 10.18821/0869-2084-2020-65-6-347-352.
Results of comparative ELISA investigation of pretreatment sPD-1 and sPD-L1 content in blood plasma of 100 gastric cancer patients at various disease stages aged 25 to 81 years are presented. Control group included 60 practically healthy donors aged 18 - 68 years. Plasma sPD-L1 concentrations did not differ between gastric cancer patients and control group, and sPD-1 levels were statistically significantly lower in patients than in healthy donors (p<0.0001). Positive correlation (R=0.38; p=0.003) was revealed between plasma sPD-1 и sPD-L1 levels in control group and negative (R= -0.26; p=0,009) - in gastric cancer patients. ROC curve revealed the best sPD-1 cut-off level (< 21 pg/ml) with 77% sensitivity and 63.3% specificity, which is not sufficient for its application as diagnostic marker. Statistically significant increase of plasma sPD-L1 from stage I to stage IIIC (R=0.50; p=0.000011) was found. Analysis of associations between the evaluated markers' levels and indices of gastric cancer expansion according to TNM system revealed statistically significant positive associations of plasma sPD -L1 levels with T (tumor invasiondepth) and N (number of affected lymph nodes) indices: R=0.33; p=0.00093, and R=0.27; p=0.0099 respectively. sPD-L1 level was significantly increased in patients with low differentiated adenocarcinoma and cricoid-cell cancer as compared to highly differentiated adenocarcinoma (p=0.02 and p=0.004 respectively); in patients with cricoid-cell cancer it was also higher than in those with moderately differentiated adenocarcinoma (p=0.043) and undifferentiated cancer (p=0.049). Plasma sPD-1 level did not depend on disease stage, TNM system indices and tumor histological structure. Thus, soluble ligand sPD-L1, but not its receptor sPD-1, plasma level is increased in patients with unfavorable clinical and morphological characteristics, may be regarded as potentially valuable prognostic factor for gastric cancer patients' survival, and probably as a predictor of anti - PD-1/PD-L1 treatment efficiency.
本文呈现了对100名年龄在25至81岁、处于不同疾病阶段的胃癌患者血浆中预处理可溶性程序性死亡受体1（sPD - 1）和可溶性程序性死亡配体1（sPD - L1）含量进行比较酶联免疫吸附测定（ELISA）的结果。对照组包括60名年龄在18 - 68岁的健康捐赠者。胃癌患者和对照组之间血浆sPD - L1浓度无差异，且患者的sPD - 1水平在统计学上显著低于健康捐赠者（p<0.0001）。在对照组中，血浆sPD - 1和sPD - L1水平呈正相关（R = 0.38；p = 0.003），而在胃癌患者中呈负相关（R = -0.26；p = 0.009）。ROC曲线显示最佳的sPD - 1临界值水平（<21 pg/ml），敏感性为77%，特异性为63.3%，这不足以将其用作诊断标志物。发现从I期到IIIC期血浆sPD - L1有统计学上的显著升高（R = 0.50；p = 0.000011）。根据TNM系统分析评估标志物水平与胃癌扩展指标之间的关联，发现血浆sPD - L1水平与T（肿瘤浸润深度）和N（受累淋巴结数量）指标有统计学上的显著正相关：分别为R = 0.33；p = 0.00093和R = 0.27；p = 0.0099。与高分化腺癌相比，低分化腺癌和环状细胞癌患者的sPD - L1水平显著升高（分别为p = 0.02和p = 0.004）；环状细胞癌患者的sPD - L1水平也高于中分化腺癌患者（p = 0.043）和未分化癌患者（p = 0.049）。血浆sPD - 1水平不依赖于疾病阶段、TNM系统指标和肿瘤组织学结构。因此，可溶性配体sPD - L1而非其受体sPD - 1的血浆水平在具有不良临床和形态学特征的患者中升高，可能被视为胃癌患者生存的潜在有价值的预后因素，并且可能是抗PD - 1/PD - L1治疗疗效的预测指标。
