Role of PD-L1 Expression in Non-Small Cell Lung Cancer and Their Prognostic Significance according to Clinicopathological Factors and Diagnostic Markers

Role of PD-L1 Expression in Non-Small Cell Lung Cancer and Their Prognostic Significance according to Clinicopathological Factors and Diagnostic Markers
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PD-L1表达在非小细胞肺癌中的作用及其根据临床病理因素和诊断标记的预后意义

DOI:
10.3390/ijms20040824
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发表时间:
2019-02-02
影响因子:
5.6
通讯作者:
Nowinska, Katarzyna
Nowinska, Katarzyna
中科院分区:
生物学2区
文献类型:
--
作者:
Pawelczyk, Konrad;Piotrowska, Aleksandra;Nowinska, Katarzyna

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背景:用于治疗非小细胞肺癌(NSCLC)的最新免疫疗法是使用针对程序性死亡配体1 (PD-L1)的单克隆抗体来抑制其与PD-1受体的相互作用。在非小细胞肺癌细胞中观察到PD-L1表达水平升高。PD-L1表达与临床病理特征之间的关系尚不清楚。因此,我们研究了这种关系,并比较了PD-L1与Ki-67、p63和TTF-1的表达水平。方法:采用866例非小细胞肺癌标本制备组织微阵列(tma),进行免疫组化(IHC)反应。采用实时荧光定量PCR (RT-PCR)检测62例NSCLC肿瘤中CD274 (PD-L1)基因表达水平与14例正常肺组织的差异。结果:32.6%的非小细胞肺癌中有PD-L1表达。PD-L1表达在高恶性分级(G) (p < 0.0001)和高淋巴结状态(pN) (p = 0.0428)中升高。仅在腺癌(AC)中,PD-L1低表达的患者比高表达组(p = 0.0332)的总生存期更长。结论:在非小细胞肺癌中,PD-L1表达似乎与肿瘤增殖和侵袭性增加以及患者生存期缩短有关,主要在AC组中。
Background: The latest immunotherapy, used in the treatment of non-small cell lung cancer (NSCLC), uses monoclonal antibodies directed against programmed death ligand 1 (PD-L1) to inhibit its interaction with the PD-1 receptor. Elevated levels of PD-L1 expression were observed on NSCLC cells. The association between PD-L1 expression and clinicopathological features is still unclear. Therefore, we examined this relationship and also compare PD-L1 expression levels with Ki-67, p63 and TTF-1. Methods: 866 samples of NSCLCs were used to prepare tissue microarrays (TMAs) on which immunohistochemical (IHC) reactions were performed. Changes in the level of CD274 (PD-L1) gene expression in 62 NSCLC tumors were tested in relation to 14 normal lung tissues by real-time PCR reactions (RT-PCR). Results: PD-L1 expression was observed in 32.6% of NSCLCs. PD-L1 expression was increased in higher malignancy grades (G) (p < 0.0001) and in higher lymph node status (pN) (p = 0.0428). The patients with low PD-L1 expression had longer overall survival compared to the group with high expression (p = 0.0332) in adenocarcinoma (AC) only. Conclusions: PD-L1 expression seems to be associated with increased tumor proliferation and aggressiveness as well as shorter patient survival in NSCLC, predominantly in the AC group.