非小细胞肺癌患者中GZMB和PD-L1的表达及两者与预后的关系

孙奥龙; 张丽柯; 徐全晓; 文鑫; 李卫阳

doi:10.16766/j.cnki.issn.1674-4152.003751

非小细胞肺癌患者中GZMB和PD-L1的表达及两者与预后的关系

doi: 10.16766/j.cnki.issn.1674-4152.003751

1.
新乡医学院附属南阳市第一人民医院呼吸与危重症医学科，河南南阳 473010
2.
新乡医学院附属南阳市第一人民医院肿瘤实验室

基金项目:

河南省医学科技攻关计划项目 LHGJ20200903

南阳市科技攻关计划项目 23KJGG215

详细信息

通讯作者:
李卫阳，E-mail：13837736267@163.com

中图分类号: R734.2 R730.43
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- 文章访问数: 19
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- 被引次数: 0
出版历程
- 收稿日期: 2023-12-12
- 网络出版日期: 2024-12-31

The expression of GZMB and PD-L1 and their relationship with prognosis in non-small cell lung patients

1.
Respiratory and Critical Care Medicine, the First People's Hospital of Nanyang City Affiliated to Xinxiang Medical College, Nanyang, Henan 473010, China

摘要

摘要: 目的分析颗粒酶B(GZMB)、程序性细胞死亡配体1(PD-L1)在非小细胞肺癌(NSCLC)组织中的表达情况及临床意义。方法收集2015年1月—2019年12月南阳市第一人民医院收治的105例NSCLC患者的癌及癌旁组织，采用免疫组化法测定GZMB、PD-L1表达，分析GZMB表达与患者临床病理特征的关系。选取2023年3—8月南阳市第一人民医院收集的30例NSCLC新鲜组织，采用RT-qPCR检测其GZMB、PD-L1 mRNA相对表达量。应用Spearman相关分析研究GZMB与PD-L1表达的相关性，绘制Kaplan-Meier曲线进行生存分析，采用Cox回归分析研究患者预后的影响因素。结果在NSCLC癌和癌旁组织中GZMB表达情况比较差异无统计学意义(P>0.05)；相比于癌旁组织，PD-L1在癌组织中高表达(P＜0.001)。Spearman相关分析显示，NSCLC组织中GZMB表达与PD-L1表达呈负相关关系(r=-0.448, P＜0.001)，且在NSCLC新鲜组织中GZMB与PD-L1 mRNA相对表达量呈负相关关系(r=-0.846, P＜0.001)。GZMB的表达与NSCLC的浸润深度、淋巴结转移、远处转移有关(P＜0.05)。105例NSCLC患者中位生存时间为39.36(1~100)个月，GZMB高表达组患者生存时间(59.15个月)长于低表达组(19.70个月)，PD-L1高表达组患者生存时间(26.67个月)短于低表达组(50.46个月)。Cox回归分析显示，GZMB、PD-L1是影响NSCLC患者预后的独立因素(P＜0.001)。结论 NSCLC患者GZMB与PD-L1的表达呈负相关关系；GZMB高表达是患者预后良好的独立保护因素，PD-L1高表达是患者预后不良的独立危险因素。
- 非小细胞肺癌 /
- 颗粒酶B /
- 程序性细胞死亡配体1 /
- 相关性 /
- 预后
Abstract: Objective To analyze the expression and clinical significance of granzyme B (GZMB) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). Methods Tumor and tumor-adjacent tissues were collected in 105 NSCLC patients from January 2015 to December 2019, and the expressions of GZMB and PD-L1 were detected to analyze the relationship between GZMB expression and clinicopathological features of NSCLC patients by immunohistochemistry. Thirty fresh NSCLC tissues collected from the First People's Hospital of Nanyang between March 2023 and August 2023, RT-qPCR was used to detect the relative expression levels of GZMB and PD-L1mRNA. GZMB and PD-L1 expression were performed by Spearman correlation analysis. Kaplan-Meier curve was drawn for survival analysis, and Cox regression was used to analyze the influencing factors of prognosis. Results There was no difference in the expression levels of GZMB between tumor and adjacent tissues in NSCLC patients (P>0.05), and PD-L1 was highly expressed in cancer tissues compared with para-cancer tissues (P < 0.001). Spearman correlation analysis revealed a negative correlation between GZMB expression and PD-L1 expression in NSCLC tissues (r=-0.448, P < 0.001). And showed a negative correlation between the relative mRNA expression levels of GZMB and PD-L1 in fresh NSCLC tissues (r=-0.846, P < 0.001). The expression of GZMB was related to the depth of invasion, lymph node metastasis, and distant metastasis of NSCLC. The median survival time of 105 patients with NSCLC was 39.36 months (1-100 months), the survival time of patients with high expression of GZMB (59.15 months) was higher than that of patients with low expression (19.70 months), and the survival time of patients with high expression of PD-L1 (26.67 months) was lower than that of patients with low expression (50.46 months). Cox regression analysis showed that GZMB and PD-L1 were independent factors affecting the prognosis of NSCLC patients (P < 0.001). Conclusion In NSCLC patients, there is a negative correlation between the expression of GZMB and PD-L1. High expression of GZMB is an independent protective factor for good prognosis in patients, while high expression of PD-L1 is an independent risk factor for poor prognosis in patients.
- Non-small cell lung cancer /
- Granzyme B /
- Programmed cell death ligand 1 /
- Correlation /
- Prognostic

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图 1 GZMB、PD-L1在NSCLC组织中的表达情况(免疫组化法，×10)

Figure 1. Expression levels of GZMB and PD-L1 proteins in NSCLC tissue (Immunohistochemical method, ×10)

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图 2 GZMB、PD-L1不同表达量与NSCLC患者总生存期的Kaplan-Meier生存曲线

Figure 2. Kaplan-Meier survival curves for different expression levels of GZMB and PD-L1 in NSCLC patients

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表 1 GZMB与PD-L1在癌组织及癌旁组织中的表达情况[例(%)]

Table 1. Expression levels of GZMB and PD-L1 in cancer and adjacent tissues [cases (%)]

组别	例数	GZMB表达		PD-L1表达
组别	例数	高表达	低表达	高表达	低表达
癌组织	105	54(51.4)	51(48.6)	55(52.4)	50(47.6)
癌旁组织	105	63(60.0)	42(40.0)	17(16.2)	88(83.8)
χ²值		1.563		30.519
P值		0.211		＜0.001

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表 2 不同GZMB表达组NSCLC患者临床病理特征比较(例)

Table 2. Comparison of clinicopathological characteristics in NSCLC patients across different GZMB expression groups (cases)

组别	例数	GZMB高表达组(n=54)	GZMB低表达组(n=51)	χ²值	P值
年龄				3.361	0.067
≥60岁	63	37	26
＜60岁	42	17	25
性别				0.001	0.970
男性	76	39	37
女性	29	15	14
吸烟史				0.496	0.481
有	54	27	29
无	51	27	22
基础病				1.960	0.658
有	43	21	22
无	62	33	29
组织学分型				2.702	0.100
鳞癌	49	21	28
腺癌	56	33	23
浸润深度				11.608	0.001
T1~2	59	39	20
T3~4	46	15	31
淋巴结转移				10.620	0.001
有	57	21	36
无	48	33	15
远处转移				7.986	0.005
有	28	8	20
无	77	46	31

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表 3 NSCLC患者预后的单因素Cox回归分析

Table 3. Univariate COX regression analysis of prognosis in NSCLC patients

变量	B	SE	Waldχ²	P值	HR(95% CI)
年龄	-0.075	0.237	0.100	0.752	0.928(0.584~1.475)
性别	-0.597	0.285	4.406	0.036	0.550(0.315~0.961)
吸烟史	0.672	0.243	7.610	0.006	1.958(1.215~3.155)
组织学类型	0.220	0.236	0.867	0.352	1.246(0.784~1.978)
基础病	-0.119	0.241	0.243	0.622	0.888(0.554~1.424)
浸润深度	1.010	0.238	18.094	＜0.001	2.747(1.724~4.375)
淋巴结转移	0.836	0.246	11.608	0.001	2.308(1.427~3.735)
远处转移	0.923	0.254	13.172	＜0.001	2.516(1.529~4.141)
PD-L1	-0.717	0.242	8.821	0.003	0.488(0.304~0.784)
GZMB	2.598	0.304	73.248	＜0.001	13.433(7.410~24.351)
注：赋值方法如下，年龄≥60岁=1，＜60岁=0；男性=1，女性=0；吸烟=1，不吸烟=0；鳞癌=1，腺癌=0；有基础病=1，无基础病=0；浸润深度T1~2=1，T3~4=0；有淋巴结转移=1，无淋巴结转移=0；有远处转移=1，无远处转移=0；PD-L1高表达=1，PD-L1低表达=0；GZMB高表达=1，GZMB低表达=0。

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表 4 NSCLC患者预后的多因素Cox回归分析

Table 4. Multivariate COX regression analysis of prognostic factors in NSCLC patients

变量	B	SE	Waldχ²	P值	HR(95% CI)
性别	0.014	0.405	0.001	0.973	1.014(0.458~2.245)
吸烟史	-0.382	0.356	1.152	0.283	0.683(0.340~1.371)
浸润深度	0.729	0.274	7.065	0.008	2.072(1.211~3.547)
淋巴结转移	0.417	0.270	2.381	0.123	1.517(0.894~2.575)
远处转移	0.558	0.282	3.908	0.048	1.747(1.005~3.038)
PD-L1	-0.852	0.273	9.750	0.002	0.427(0.250~0.728)
GZMB	2.875	0.372	59.765	＜0.001	17.722(8.550~36.733)

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