PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer
Abstract Background Programmed cell death ligand-1 (PD-L1) and ligand-2 (PD-L2) interaction with programmed cell death protein-1 (PD-1) represent an immune-inhibiting checkpoint mediating immune evasion and is, accordingly, an important target for blockade-based immunotherapy in cancer. In non-small...
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doaj-a90dd24ce10c4b48a6c7a4861ea35a2a2020-11-25T03:08:39ZengWileyCancer Communications2523-35482019-06-0139111410.1186/s40880-019-0376-6PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancerTrine Vilsbøll Larsen0Dianna Hussmann1Anders Lade Nielsen2Department of Biomedicine, Aarhus UniversityDepartment of Biomedicine, Aarhus UniversityDepartment of Biomedicine, Aarhus UniversityAbstract Background Programmed cell death ligand-1 (PD-L1) and ligand-2 (PD-L2) interaction with programmed cell death protein-1 (PD-1) represent an immune-inhibiting checkpoint mediating immune evasion and is, accordingly, an important target for blockade-based immunotherapy in cancer. In non-small-cell lung cancer (NSCLC), improved understanding of PD-1 checkpoint blockade-responsive biology and identification of biomarkers for prediction of a clinical response to immunotherapy is warranted. Thus, in the present study, we systematically described PD-L1 and PD-L2 expression correlated genes in NSCLC. Methods We performed comparative retrospective analyses to identify PD-L1 and PD-L2 mRNA expression correlated genes in NSCLC. For this, we examined available datasets from the cancer cell line encyclopedia (CCLE) project lung non-small-cell (Lung_NSC) and the cancer genome atlas (TCGA) projects lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results Analysis of the CCLE dataset Lung_NSC identified expression correlation between PD-L1 and PD-L2. Moreover, we identified expression correlation between 489 genes and PD-L1, 191 genes and PD-L2, and 111 genes for both. PD-L1 and PD-L2 also expression correlated in TCGA datasets LUAD and LUSC. In LUAD, we identified expression correlation between 257 genes and PD-L1, 914 genes and PD-L2, and 211 genes for both. In LUSC, we identified expression correlation between 26 genes and PD-L1, 326 genes and PD-L2, and 13 genes for both. Only a few genes expression correlated with PD-L1 and PD-L2 across the CCLE and TCGA datasets. Expression of Interferon signaling-involved genes converged in particular with the expression correlated genes for PD-L1 in Lung_NSC, for PD-L2 in LUSC, and for both PD-L1 and PD-L2 in LUAD. In LUSC, PD-L1, and to a lesser extent PD-L2, expression correlated with chromosome 9p24 localized genes, indicating a chromosome 9p24 topologically associated domain as an important driver of in particular LUSC PD-L1 expression. Expression correlation analyses of the PD-L1 and PD-L2 receptors programmed cell death protein-1 (PD-1), Cluster of differentiation 80 (CD80), and Repulsive guidance molecule B (RGMB) showed that PD-1 and CD80 expression correlated with both PD-L1 and PD-L2 in LUAD. CD80 expression correlated with PD-L2 in LUSC. Conclusions We present gene signatures associated with PD-L1 and PD-L2 mRNA expression in NSCLC which could possess importance in relation to understand PD-1 checkpoint blockade-responsive biology and development of gene signature based biomarkers for predicting clinical responses to immunotherapy.http://link.springer.com/article/10.1186/s40880-019-0376-6Non-small-cell lung cancerBiomarkerImmunotherapyImmune checkpointsInterferonChr9p24 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Trine Vilsbøll Larsen Dianna Hussmann Anders Lade Nielsen |
spellingShingle |
Trine Vilsbøll Larsen Dianna Hussmann Anders Lade Nielsen PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer Cancer Communications Non-small-cell lung cancer Biomarker Immunotherapy Immune checkpoints Interferon Chr9p24 |
author_facet |
Trine Vilsbøll Larsen Dianna Hussmann Anders Lade Nielsen |
author_sort |
Trine Vilsbøll Larsen |
title |
PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer |
title_short |
PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer |
title_full |
PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer |
title_fullStr |
PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer |
title_full_unstemmed |
PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer |
title_sort |
pd-l1 and pd-l2 expression correlated genes in non-small-cell lung cancer |
publisher |
Wiley |
series |
Cancer Communications |
issn |
2523-3548 |
publishDate |
2019-06-01 |
description |
Abstract Background Programmed cell death ligand-1 (PD-L1) and ligand-2 (PD-L2) interaction with programmed cell death protein-1 (PD-1) represent an immune-inhibiting checkpoint mediating immune evasion and is, accordingly, an important target for blockade-based immunotherapy in cancer. In non-small-cell lung cancer (NSCLC), improved understanding of PD-1 checkpoint blockade-responsive biology and identification of biomarkers for prediction of a clinical response to immunotherapy is warranted. Thus, in the present study, we systematically described PD-L1 and PD-L2 expression correlated genes in NSCLC. Methods We performed comparative retrospective analyses to identify PD-L1 and PD-L2 mRNA expression correlated genes in NSCLC. For this, we examined available datasets from the cancer cell line encyclopedia (CCLE) project lung non-small-cell (Lung_NSC) and the cancer genome atlas (TCGA) projects lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results Analysis of the CCLE dataset Lung_NSC identified expression correlation between PD-L1 and PD-L2. Moreover, we identified expression correlation between 489 genes and PD-L1, 191 genes and PD-L2, and 111 genes for both. PD-L1 and PD-L2 also expression correlated in TCGA datasets LUAD and LUSC. In LUAD, we identified expression correlation between 257 genes and PD-L1, 914 genes and PD-L2, and 211 genes for both. In LUSC, we identified expression correlation between 26 genes and PD-L1, 326 genes and PD-L2, and 13 genes for both. Only a few genes expression correlated with PD-L1 and PD-L2 across the CCLE and TCGA datasets. Expression of Interferon signaling-involved genes converged in particular with the expression correlated genes for PD-L1 in Lung_NSC, for PD-L2 in LUSC, and for both PD-L1 and PD-L2 in LUAD. In LUSC, PD-L1, and to a lesser extent PD-L2, expression correlated with chromosome 9p24 localized genes, indicating a chromosome 9p24 topologically associated domain as an important driver of in particular LUSC PD-L1 expression. Expression correlation analyses of the PD-L1 and PD-L2 receptors programmed cell death protein-1 (PD-1), Cluster of differentiation 80 (CD80), and Repulsive guidance molecule B (RGMB) showed that PD-1 and CD80 expression correlated with both PD-L1 and PD-L2 in LUAD. CD80 expression correlated with PD-L2 in LUSC. Conclusions We present gene signatures associated with PD-L1 and PD-L2 mRNA expression in NSCLC which could possess importance in relation to understand PD-1 checkpoint blockade-responsive biology and development of gene signature based biomarkers for predicting clinical responses to immunotherapy. |
topic |
Non-small-cell lung cancer Biomarker Immunotherapy Immune checkpoints Interferon Chr9p24 |
url |
http://link.springer.com/article/10.1186/s40880-019-0376-6 |
work_keys_str_mv |
AT trinevilsbølllarsen pdl1andpdl2expressioncorrelatedgenesinnonsmallcelllungcancer AT diannahussmann pdl1andpdl2expressioncorrelatedgenesinnonsmallcelllungcancer AT andersladenielsen pdl1andpdl2expressioncorrelatedgenesinnonsmallcelllungcancer |
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