Chinese General Practice ›› 2022, Vol. 25 ›› Issue (18): 2262-2267.DOI: 10.12114/j.issn.1007-9572.2021.02.080

Special Issue: 肿瘤最新文章合集

• Original Research • Previous Articles     Next Articles

Expression of Programmed Death Ligand 1 and Density of CD8+ Tumor-infiltrating T-lymphocytes in Gastric Cancer Tissues and Their Relationship with Clinicopathological Characteristics and Prognosis of Patients with Gastric Cancer

  

  1. Nanyang First People's Hospital/Key Laboratory of Tumor Molecular Biology Medicine of Henan Province, Nanyang 473000, China
  • Received:2021-09-27 Revised:2022-02-24 Published:2022-06-20 Online:2022-04-22
  • Contact: Quanxiao XU
  • About author:
    ZHANG L K, MA L, SHI F Y, et al. Expression of programmed death ligand 1 and density of CD8+ tumor-infiltrating T-lymphocytes in gastric cancer tissues and their relations with clinicopathological characteristics and prognosis of patients with gastric cancer[J]. Chinese General Practice, 2022, 25 (18) : 2262-2267.

胃癌组织细胞程序性死亡配体1表达情况和CD8+肿瘤浸润T淋巴细胞密度及其与患者临床病理特征和预后的关系研究

  

  1. 473000 河南省南阳市第一人民医院 河南省肿瘤分子生物学医学重点实验室
  • 通讯作者: 徐全晓
  • 作者简介:
    张丽柯,马磊,史芳瑜,等.胃癌组织细胞程序性死亡配体1表达情况和CD8+肿瘤浸润T淋巴细胞密度及其与患者临床病理特征和预后的关系研究[J].中国全科医学,2022,25(18):2262-2267.[www.chinagp.net] 作者贡献:张丽柯负责文献的检索、研究的设计及文章撰写;马磊、史芳瑜进行数据收集、采集、清洗和统计学分析,并负责制作图表;徐全晓对文章知识性内容进行批判性审阅并提供材料支持,进行文章质量控制和审校,对文章整体负责。所有作者确认了论文最终稿。
  • 基金资助:
    2020年河南省医学科技攻关计划(LHGJ20200903)

Abstract:

Background

At present, whether the expression of programmed death ligand 1 (PD-L1) and the density of CD8+ tumor-infiltrating T lymphocytes (TILs) in gastric cancer tissue can be used as prognostic indicators for gastric cancer patients has been still unclear.

Objective

To analyze the expression of PD-L1 and density of CD8+ TILs in gastric cancer tissues and their relations with clinicopathological characteristics and prognosis of patients with gastric cancer.

Methods

A 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 quantitative polymerase chain reaction, the density of CD8+ TILs in gastric cancer tissue was detected by immunohistochemical methods. The relations of the relative expression quantity of PD-L1 mRNA and the density of CD8+ TILs in gastric cancer tissue with the clinicopathological characteristics of patients with gastric cancer was analyzed; the correlation between the relative expression quantity of PD-L1 mRNA and the density of CD8+ 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 PD-L1 mRNA was 3.1 in gastric cancer tissue, the average number of CD8+ 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 relative expression quantity of PD-L1 mRNA equal or over 3.1, n=52) , low-density group (with number of CD8+ TILs less than 31, n=55) and high-density group (with number of CD8+ 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 expression quantity of PD-L1 mRNA was negatively correlated with density of CD8+ 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, 95%CI (1.632, 5.045) 〕and low-density CD8+ TILs〔HR=2.158, 95%CI (1.854, 4.632) 〕were independent risk factors of poor prognosis of patients with gastric cancer (P<0.05) .

Conclusion

High level of PD-L1 mRNA and low density of CD8+ 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, CD8-positive T-lymphocytes, Disease attributes, Prognosis

摘要:

背景

目前,胃癌组织细胞程序性死亡配体1(PD-L1)表达情况和CD8+肿瘤浸润T淋巴细胞(TILs)密度是否可作为胃癌患者预后的评估指标尚不明确。

目的

分析胃癌组织PD-L1表达情况、CD8+ TILs密度及其与患者临床病理特征和预后的关系。

方法

选择2016年1月至2018年3月在南阳市第一人民医院行手术治疗的胃癌患者125例,采用实时荧光定量反转录聚合酶链反应检测其胃癌组织PD-L1 mRNA相对表达量,采用免疫组化方法检测其胃癌组织CD8+ TILs密度。分析胃癌组织PD-L1 mRNA相对表达量、CD8+ TILs密度与患者临床病理特征的关系;胃癌组织PD-L1 mRNA相对表达量与CD8+ TILs密度的相关性分析采用Pearson相关分析;通过电话随访至术后36个月,以患者死亡或失访为终点事件,绘制Kaplan-Meier曲线以进行生存分析;胃癌患者预后的影响因素分析采用单因素和多因素Cox回归分析。

结果

所有患者胃癌组织平均PD-L1 mRNA相对表达量为3.1,癌巢内平均CD8+ TILs数量为36个,最终归为低水平组73例(PD-L1 mRNA相对表达量<3.1)和高水平组52例(PD-L1 mRNA相对表达量≥3.1),低密度组55例(CD8+ TILs数量<36个)和高密度组70例(CD8+ TILs≥36个)。低水平组与高水平组患者淋巴结转移、脉管侵犯、腹膜转移情况比较,差异有统计学意义(P<0.05);低密度组与高密度组患者浸润深度、淋巴结转移、脉管侵犯、腹膜转移情况比较,差异有统计学意义(P<0.05)。Pearson相关分析结果显示,胃癌组织PD-L1 mRNA相对表达量与CD8+ TILs密度呈负相关(r=-0.412,P<0.001)。中位随访时间为36.0个月,125例患者中预后不良37例,预后良好88例;低水平组与高水平组、低密度组与高密度组患者Kaplan-Meier曲线比较,差异均有统计学意义(P<0.05)。多因素Cox回归分析结果显示,高水平PD-L1 mRNA〔HR=3.021,95%CI(1.632,5.045)〕、低密度CD8+ TILs〔HR=2.158,95%CI(1.854,4.632)〕为胃癌患者预后不良的独立危险因素(P<0.05)。

结论

高水平PD-L1 mRNA、低密度CD8+ TILs均是胃癌患者预后不良的独立危险因素,有望成为胃癌患者预后不良的生物标志物。

关键词: 胃癌, 细胞程序性死亡配体1, CD8阳性T淋巴细胞, 疾病特征, 预后