Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma
Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma
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DOI：
10.1016/j.ejca.2018.06.020
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发表时间：
2018-09-01
影响因子：
8.4
通讯作者：
Maehara, Yoshihiko
中科院分区：
文献类型：
--
作者：
Kozuma, Yuka;Takada, Kazuki;Maehara, Yoshihiko
背景：吲哚胺2,3-双加氧酶1 （IDO1）是一种免疫抑制效应物，其表达与多种癌症类型的预后有关。在这里，我们研究了IDO1在肺腺癌中的表达与患者预后和临床病理特征的关系，包括程序性细胞死亡配体1 （PD-L1）的表达。材料和方法：本研究采用免疫组化方法检测427例手术切除的原发性肺腺癌标本中IDO1和PD-L1的表达，采用酶联免疫吸附法和流式细胞术检测肺腺癌细胞株中IDO1和PD-L1蛋白的表达，采用实时逆转录酶聚合酶链反应法检测信使RNA水平。结果：IDO1在1%截止时与260例患者（60.9%）表达，在50%截止时与63例患者（14.8%）表达。145例患者（34.0%）的组织PD-L1呈阳性，截止率为1%。多因素分析显示，>= 1%的IDO1阳性与较高的肿瘤分级、血管侵袭和PD-L1表达显著相关。123例患者（28.8%）共表达IDO1和PD-L1蛋白，并且共表达的肿瘤比其中一种或两种蛋白均阳性的肿瘤表现出更多的恶性特征。在多变量分析中，IDO1和PD-L1的共表达与较短的无病生存期和总生存期显著相关。干扰素- γ和转化生长因子- β处理后，两种蛋白在肺腺癌细胞系中均上调。结论：这些结果提示IDO1和PD-L1的共同表达可能决定了肺腺癌的侵袭性形式。(C) 2018 Elsevier Ltd.版权所有。
Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here, we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression.Materials and methods: In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry, and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis.Results: IDO1 was expressed in 260 patients (60.9%) at 1% cut-off and 63 patients (14.8%) at 50% cut-off. Tissues from 145 patients (34.0%) were positive for PD-L1 using the cut-off of 1%. Multivariate analysis showed that >= 1% IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-gamma and transforming growth factor-beta.Conclusion: These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma. (C) 2018 Elsevier Ltd. All rights reserved.