Page 90 - 中国全科医学2022-18

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total of 125 gastric cancer patients underwent surgical treatment in Nanyang First People's Hospital from January 2016 to March
2018 were selected，and the expression level of PD-L1 mRNA in gastric cancer tissue was detected by real-time fluorescence
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quantitative polymerase chain reaction，the density of CD 8 TILs in gastric cancer tissue was detected by immunohistochemical
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methods. The relations of the relative expression quantity of PD-L1 mRNA and the density of CD 8 TILs in gastric cancer tissue
with the clinicopathological characteristics of patients with gastric cancer was analyzed；the correlation between the relative
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expression quantity of PD-L1 mRNA and the density of CD 8 TILs in gastric cancer tissue was analyzed by Pearson correlation
analysis；telephone follow-up was conduct till to 36 months after operation，taking death or loss to follow-up as outcome event，
Kaplan-Meier survivorship curve was drawn to conduct survival analysis；univariate and multivariate Cox regression analysis was
used to analyze the influencing factors of prognosis of gastric cancer patients. Results The average relative expression quantity of
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PD-L1 mRNA was 3.1 in gastric cancer tissue，the average number of CD 8 TILs was 36 in cancer nests，thus the 125 patients
were divided into low-level group（with relative expression quantity of PD-L1 mRNA less than 3.1，n=73），high-level group（with
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relative expression quantity of PD-L1 mRNA equal or over 3.1，n=52），low-density group（with number of CD 8 TILs less than
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31，n=55）and high-density group（with number of CD 8 TILs equal or over 31，n=70）. There were significant differences
in lymph node metastasis，vascular invasion and peritoneal metastasis between the the low-level group and high-level group
（P<0.05），so as in depth of infiltration，incidence of lymphatic metastasis，vascular invasion and peritoneal metastasis
between the the low-density group and high-density group（P<0.05）. Pearson correlation analysis showed that the relative
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expression quantity of PD-L1 mRNA was negatively correlated with density of CD 8 TILs in gastric cancer tissue（r=-0.412，
P<0.001）. We found 88 cases with good prognosis and 37 cases with poor prognosis，with the medium time of follow-up of 36
months；there was significant difference in Kaplan-Meier curve between low-level and high-level groups，low-density and high-
density groups，respectively（P<0.05）. Multivariate Cox regression analysis showed that high-level PD-L1 mRNA〔HR=3.021，
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95%CI（1.632，5.045）〕and low-density CD 8 TILs〔HR=2.158，95%CI（1.854，4.632）〕were independent risk factors
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of poor prognosis of patients with gastric cancer（P<0.05）. Conclusion High level of PD-L1 mRNA and low density of CD 8
TILs are independent risk factors of poor prognosis in gastric cancer patients，which are expected to be biomarkers for poor
prognosis in gastric cancer patients.
【Key words】 Stomach neoplasms；Programmed cell death ligand 1；CD 8 -positive T-lymphocytes；Disease
attributes；Prognosis

胃癌是全球范围内第五大常见恶性肿瘤，而在癌症 本研究价值：
相关死亡原因中，胃癌位居第三 ［1］ 。近年研究表明，
目前，用于评估胃癌进展情况和患者预后的常用
多数胃癌与幽门螺杆菌、Epstein-Barr（EB）病毒感染
指标〔如国际妇产科联盟（FIGO）分期〕并未考虑
及慢性炎症有关，而靶向免疫系统治疗是一种十分有 患者整体免疫状态，而胃癌组织细胞程序性死亡配体
应用前景的胃癌治疗方法 ［2-4］ ；细胞程序性死亡配体 1 +
1（PD-L1）表达情况和CD 8 肿瘤浸润T淋巴细胞（TILs）
（programmed cell death ligand 1，PD-L1）与其受体细
密度是否可用于评估胃癌患者预后尚不明确。本研究
胞程序性死亡受体 1（programmed cell death 1，PD-1） +
证实高水平 PD-L1 mRNA、低密度 CD 8 TILs 均是胃
结合后可抑制 T 细胞迁移、增殖及细胞毒性递质分泌，
癌患者预后不良的独立危险因素，有望成为胃癌患者
最终通过减弱效应 T 细胞功能而限制其对肿瘤细胞的杀 预后不良的生物标志物。
伤作用 ［5］ 。
PD-L1 通常在免疫细胞（如巨噬细胞和树突状细 密度及其与患者临床病理特征和预后的关系。
胞）中表达，在多种肿瘤（如黑色素瘤、非小细胞肺癌、 1 对象与方法
结肠癌）细胞中亦有表达 ［6-8］ 。研究表明，肿瘤细胞 1.1 研究对象 选择 2016 年 1 月至 2018 年 3 月在南
对 PD-L1 的调节机制主要包括内在免疫抵抗和适应性 阳市第一人民医院行手术治疗的胃癌患者 125 例，其中
抵抗，肿瘤细胞中 PD-L1 表达上调并与肿瘤浸润 T 淋 男 76 例、女 49 例；年龄 40~65 岁，平均年龄（57.1±8.2）
巴细胞（tumour-infiltrating lymphoeytes，TILs）表达的 岁。纳入标准：（1）经胃镜活检和术后病理检查确诊
PD-1 相互作用，从而负向调节免疫反应，造成肿瘤免 为胃癌；（2）行胃癌根治术；（3）术前未接受过新辅
疫逃逸 ［9］ 。因此，了解肿瘤细胞免疫状态对评估患者 助化疗；（4）初次诊断。排除标准：（1）其他恶性肿
预后和免疫治疗的生物标志物筛选均有一定指导价值。 瘤；（2）感染性疾病；（3）免疫系统疾病。本研究经
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本研究旨在分析胃癌组织 PD-L1 表达情况、CD 8 TILs 南阳市第一人民医院伦理委员会审核批准（批准号：