Promoter hypomethylation of NY-ESO-1, association with clinicopathological features and PD-L1 expression in non-small cell lung cancer

Oncotarget
Anderly C ChüehThomas John

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 progno...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Oncology·Susana Romero-GarciaAngeles Carlos-Reyes
Apr 11, 2020·International Journal of Molecular Sciences·Achamaporn PunnanitinontSantosh K Patnaik
Feb 15, 2020·Pathology, Research and Practice·Zhu LinglingZhou Qinghua
Apr 27, 2021·Pathology International·Tadashi SakaneHiroshi Inagaki
Jul 1, 2021·Trends in Molecular Medicine·Giulia LucibelloPatrick Brest

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Methods Mentioned

BETA
transfection
electrophoresis
PCR

Clinical Trials Mentioned

NCT01928576

Software Mentioned

GraphPad
R
Prism
STATA

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