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Title: Promoter hypomethylation of NY-ESO-1, association with clinicopathological features and PD-L1 expression in non-small cell lung cancer.
Austin Authors: Chüeh, Anderly C;Liew, Mun-Sem;Russell, Prudence A;Walkiewicz, Marzena;Jayachandran, Aparna;Starmans, Maud H W;Boutros, Paul C;Wright, Gavin;Barnett, Stephen A ;Mariadason, John M ;John, Thomas 
Affiliation: Department of Thoracic Surgery, Austin Health, Heidelberg, Victoria, Australia
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada
Department of Thoracic Oncology, St Vincent's Hospital, Victoria, Australia
Ludwig Institute for Cancer Research, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Anatomical Pathology, St Vincent's Hospital, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Informatics and Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Canada
Department of Medical Biophysics, University of Toronto, Toronto, Canada
Issue Date: 26-Sep-2017 2017-05-23
Publication information: Oncotarget 2017; 8(43): 74036-74048
Abstract: Cancer-Testis antigens (CTA) are immunogenic molecules with normal tissue expression restricted to testes but with aberrant expression in up to 30% of non-small cell lung cancers (NSCLCs). Regulation of CTA expression is mediated in part through promoter DNA methylation. Recently, immunotherapy has altered treatment paradigms in NSCLC. Given its immunogenicity and ability to be re-expressed through demethylation, NY-ESO-1 promoter methylation, protein expression and its association with programmed death receptor ligand-1 (PD-L1) expression and clinicopathological features were investigated. Lung cancer cell line demethylation resulting from 5-Aza-2'-deoxycytidine treatment was associated with both NY-ESO-1 and PD-L1 re-expression in vitro but not increased chemosensitivity. NY-ESO-1 hypomethylation was observed in 15/94 (16%) of patient samples and associated with positive protein expression (P < 0.0001). In contrast, PD-L1 expression was observed in 50/91 (55%) but strong expression in only 12/91 (13%) cases. There was no association between NY-ESO-1 and PD-L1 expression, despite resultant re-expression of both by 5-Aza-2'-deoxycytidine. Importantly, NY-ESO-1 hypomethylation was found to be an independent marker of poor prognosis in patients not treated with chemotherapy (HR 3.59, P = 0.003) in multivariate analysis. In patients treated with chemotherapy there were no differences in survival associated with NY-ESO-1 hypomethylation. Collectively, these results provided supporting evidence for the potential use of NY-ESO-1 hypomethylation as a prognostic biomarker in stage 3 NSCLCs. In addition, these data highlight the potential to incorporate demethylating agents to enhance immune activation, in tumours currently devoid of immune infiltrates and expression of immune checkpoint genes.
DOI: 10.18632/oncotarget.18198
PubMed URL: 29088766
Type: Journal Article
Subjects: NY-ESO-1
lung cancer
promoter methylation
Appears in Collections:Journal articles

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