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

doi:10.12114/j.issn.1007-9572.2021.02.080

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

Special Issue: 肿瘤最新文章合辑；消化系统疾病最新文章合辑

• 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

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

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

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

Like ZHANG,Lei MA,Fangyu SHI, et al. 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[J]. Chinese General Practice, 2022, 25(18): 2262-2267. DOI: 10.12114/j.issn.1007-9572.2021.02.080.
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. DOI: 10.12114/j.issn.1007-9572.2021.02.080.

Figures/Tables 5

References 22

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临床病理特征		PD-L1 mRNA相对表达量				CD₈⁺ TILs密度
临床病理特征		低水平组（n=73）	高水平组（n=52）	χ²（t）值	P值	低密度组（n=55）	高密度组（n=70）	χ²（t）值	P值
年龄（±s，岁）		56.8±6.3	57.4±5.2	-0.563^a	0.574	56.0±4.5	57.8±7.5	-1.571^a	0.119
性别〔n（%）〕				0.946	0.331			0.332	0.565
	男	47（64.4）	29（55.8）			35（63.6）	41（58.6）
	女	26（35.6）	23（44.2）			20（36.4）	29（41.4）
手术类型〔n（%）〕				0.809	0.368			0.315	0.575
	腹腔镜手术	62（84.9）	47（90.4）			49（89.1）	60（85.7）
	开腹手术	11（15.1）	5（9.6）			6（10.9）	10（14.3）
分化程度〔n（%）〕				2.946	0.086			0.1915	0.339
	分化	45（61.6）	24（46.2）			33（60.0）	36（51.4）
	未分化	28（38.4）	28（53.8）			22（40.0）	34（48.6）
浸润深度〔n（%）〕				0.743	0.389			11.927	0.001
	T₁~T₂	49（67.1）	31（59.6）			26（47.3）	54（77.1）
	T₃~T₄	24（32.9）	21（40.4）			29（52.7）	16（22.9）
淋巴结转移〔n（%）〕				6.671	0.010			8.406	0.004
	无	20（27.4）	26（50.0）			28（50.9）	18（25.7）
	有	53（72.6）	26（50.0）			27（49.1）	52（74.3）
脉管侵犯〔n（%）〕				6.290	0.012			6.186	0.013
	无	55（75.3）	28（53.8）			30（54.5）	53（75.7）
	有	18（24.7）	24（46.2）			25（45.5）	17（24.3）
腹膜转移〔n（%）〕				4.283	0.038			5.263	0.022
	无	65（89.0）	39（75.0）			41（74.5）	63（90.0）
	有	8（11.0）	13（25.0）			14（25.5）	7（10.0）

临床病理特征		PD-L1 mRNA相对表达量				CD₈⁺ TILs密度
临床病理特征		低水平组（n=73）	高水平组（n=52）	χ²（t）值	P值	低密度组（n=55）	高密度组（n=70）	χ²（t）值	P值
年龄（±s，岁）		56.8±6.3	57.4±5.2	-0.563^a	0.574	56.0±4.5	57.8±7.5	-1.571^a	0.119
性别〔n（%）〕				0.946	0.331			0.332	0.565
	男	47（64.4）	29（55.8）			35（63.6）	41（58.6）
	女	26（35.6）	23（44.2）			20（36.4）	29（41.4）
手术类型〔n（%）〕				0.809	0.368			0.315	0.575
	腹腔镜手术	62（84.9）	47（90.4）			49（89.1）	60（85.7）
	开腹手术	11（15.1）	5（9.6）			6（10.9）	10（14.3）
分化程度〔n（%）〕				2.946	0.086			0.1915	0.339
	分化	45（61.6）	24（46.2）			33（60.0）	36（51.4）
	未分化	28（38.4）	28（53.8）			22（40.0）	34（48.6）
浸润深度〔n（%）〕				0.743	0.389			11.927	0.001
	T₁~T₂	49（67.1）	31（59.6）			26（47.3）	54（77.1）
	T₃~T₄	24（32.9）	21（40.4）			29（52.7）	16（22.9）
淋巴结转移〔n（%）〕				6.671	0.010			8.406	0.004
	无	20（27.4）	26（50.0）			28（50.9）	18（25.7）
	有	53（72.6）	26（50.0）			27（49.1）	52（74.3）
脉管侵犯〔n（%）〕				6.290	0.012			6.186	0.013
	无	55（75.3）	28（53.8）			30（54.5）	53（75.7）
	有	18（24.7）	24（46.2）			25（45.5）	17（24.3）
腹膜转移〔n（%）〕				4.283	0.038			5.263	0.022
	无	65（89.0）	39（75.0）			41（74.5）	63（90.0）
	有	8（11.0）	13（25.0）			14（25.5）	7（10.0）

变量	赋值
年龄	实测值
性别	女=0，男=1
手术类型	开腹手术=0，腹腔镜手术=1
分化程度	分化=0，未分化=1
浸润深度	T₁~T₂=0，T₃~T₄=1
淋巴结转移	无=0，有=1
脉管侵犯	无=0，有=1
腹膜转移	无=0，有=1
PD-L1 mRNA相对表达量	低水平=0，高水平=1
CD₈⁺ TILs密度	高密度=0，低密度=1
预后	良好=0，不良=1

变量	赋值
年龄	实测值
性别	女=0，男=1
手术类型	开腹手术=0，腹腔镜手术=1
分化程度	分化=0，未分化=1
浸润深度	T₁~T₂=0，T₃~T₄=1
淋巴结转移	无=0，有=1
脉管侵犯	无=0，有=1
腹膜转移	无=0，有=1
PD-L1 mRNA相对表达量	低水平=0，高水平=1
CD₈⁺ TILs密度	高密度=0，低密度=1
预后	良好=0，不良=1

变量	单因素Cox回归分析					多因素Cox回归分析
变量	β	SE	Wald χ²值	P值	HR（95%CI）	β	SE	Wald χ²值	P值	HR（95%CI）
年龄	0.425	0.299	2.012	0.014	1.452（1.087，3.256）	0.635	0.678	0.878	0.076	1.032（0.847，1.415）
性别	0.859	0.707	1.475	0.087	1.526（0.895，1.854）	—	—	—	—	—
手术类型	-1.230	0.562	4.790	0.105	0.814（0.725，1.024）	—	—	—	—	—
分化程度	-0.474	0.466	1.036	0.074	0.698（0.529，1.241）	—	—	—	—	—
浸润深度	2.147	0.611	12.362	<0.001	11.458（3.584，21.021）	2.047	0.640	10.215	<0.001	8.256（2.367，15.021）
淋巴结转移	0.356	0.320	1.236	0.085	1.104（0.896，1.352）	—	—	—	—	—
脉管侵犯	3.521	0.900	15.326	<0.001	8.145（3.625，14.363）	3.605	1.012	12.682	<0.001	6.150（3.071，12.063）
腹膜转移	2.241	0.817	7.526	0.004	3.452（1.632，8.635）	2.307	0.839	7.526	0.017	2.856（1.418，6.328）
PD-L1 mRNA相对表达量	3.251	1.576	5.263	0.008	4.256（1.625，6.302）	1.632	0.705	5.362	0.020	3.021（1.632，5.045）
CD₈⁺ TILs密度	2.306	1.207	3.652	0.015	3.652（1.147，5.065）	2.149	0.941	5.214	0.032	2.158（1.854，4.632）

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

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

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