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PD-L1 protein expression in non-small-cell lung cancer and its relationship with the hypoxia-related signaling pathways: A study based on immunohistochemistry and RNA sequencing data

Authors
Koh, YW; Lee, SJ; Han, JH; Haam, S; Jung, J; Lee, HW
Citation
Lung cancer (Amsterdam, Netherlands), 129. : 41-47, 2019
Journal Title
Lung cancer (Amsterdam, Netherlands)
ISSN
0169-50021872-8332
Abstract
OBJECTIVES: Therapies that target programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Hypoxia-related genes are also important regulators of PD-L1, and the role of PD-L1 in NSCLC is still not clear. The objective of this study was to investigate PD-L1 expression and its correlation with hypoxic-inducible factor 1alpha (HIF1A), vascular endothelial growth factor A (VEGFA), glucose transporter 1 (GLUT1), and carbonic anhydrase 9 (CAIX) expression in NSCLC patients. The association between PD-L1 expression and survival was also determined.
MATERIALS AND METHODS: PD-L1/protein expression was evaluated in 295 resected NSCLCs and its correlation with HIF1A, VEGFA, GLUT1, CAIX expression and survival was determined based on immunohistochemical and RNA sequencing data obtained from The Cancer Genome Atlas (TCGA) database.
RESULTS: PD-L1 protein expression was significantly correlated with HIF1A, VEGFA, GLUT1, and CAIX expression only in adenocarcinoma when a 10% or a 50% cut-off was used. PD-L1 mRNA expression was also significantly correlated with HIF1A, VEGFA, GLUT1, and CAIX expression in adenocarcinoma. Univariate analysis revealed that HIF1A expression was associated with poor recurrence-free survival (RFS), and GLUT1 was associated with poor overall survival (OS) and RFS. GLUT1 was an independent prognostic factor for OS in multivariate analysis of immunohistochemical and TCGA data (p = 0.024 and 0.029, respectively). Patients with low expression of both PD-L1 and GLUT1 had longer OS than other patterns in immunohistochemical and TCGA data (p = 0.003 and 0.051, respectively).
CONCLUSIONS: PD-L1 protein and mRNA expression were correlated with HIF1A, VEGFA, GLUT1, and CAIX expression in adenocarcinoma alone. Low expression of GLUT1 and low expression of both PD-L1 and GLUT1 were associated with improved prognosis. Our findings support the rationale for co-targeting hypoxia-related genes and PD-L1 in cancer therapy. Expression of hypoxia-related genes may be helpful in selecting patients appropriate for PD-L1 therapy.
Keywords
Carbonic anhydrase 9Glucose transporter 1Hypoxic-inducible factor 1αNon-small-cell lung cancerProgrammed death-ligand 1Vascular endothelial growth factor A
MeSH terms
AdultAgedAged, 80 and overB7-H1 Antigen / metabolism*Carbonic Anhydrase IX / geneticsCarbonic Anhydrase IX / metabolismCarcinoma, Non-Small-Cell Lung / immunologyCarcinoma, Non-Small-Cell Lung / metabolism*FemaleGlucose Transporter Type 1 / geneticsGlucose Transporter Type 1 / metabolismHumansHypoxia / immunologyHypoxia / metabolism*Hypoxia-Inducible Factor 1, alpha Subunit / geneticsHypoxia-Inducible Factor 1, alpha Subunit / metabolismImmunohistochemistryLung Neoplasms / immunologyLung Neoplasms / metabolism*MaleMiddle AgedPrognosisProgrammed Cell Death 1 Receptor / metabolism*Sequence Analysis, RNASignal TransductionVascular Endothelial Growth Factor A / geneticsVascular Endothelial Growth Factor A / metabolism
DOI
10.1016/j.lungcan.2019.01.004
PMID
30797490
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Nuclear Medicine & Molecular Imaging
Journal Papers > School of Medicine / Graduate School of Medicine > Thoracic & Cardiovascular Surgery
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
AJOU Authors
고, 영화이, 수진한, 재호함, 석진정, 준호이, 현우
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