Detailed analysis of adenosine A2a receptor (ADORA2A ) and CD73 (5'-nucleotidase, ecto, NT5E ) methylation and gene expression in head and neck squamous cell carcinoma patients

Oncoimmunology
Timo J VogtDimo Dietrich

Abstract

Background: The adenosine A2a receptor (A2aR) and the adenosine synthesizing enzyme CD73 have recently evolved as a novel immunotherapeutic target. However, little is known about epigenetic modification of the encoding genes ADORA2A and NT5E. Methods: In the present study, we evaluated methylation at 23 loci of ADORA2A and 17 loci of NT5E with regard to transcriptional activity, human papilloma virus (HPV) status, immune cell infiltration, and outcome in a cohort of 279 head and neck squamous carcinoma (HNSCC) patients obtained from The Cancer Genome Atlas (TCGA). Methylation and mRNA expression were generated by the Infinium HumanMethylation450 BeadChip and Illumina HiSeq 2000 RNA Sequencing Version 2 analysis (Illumina, Inc., San Diego, CA, USA). HPV status was assessed by RNA-Seq data analysis of the viral genes E6 and E7. Results: Thirteen out of 23 ADORA2A loci and 15/17 NT5E loci were significantly correlated with mRNA levels (p < 0.05). Inverse correlations were predominately found in promoter regions, while positive correlations were more profound at intragenic loci. ADORA2A hypermethylation was significantly associated with poor overall survival (OS, p ≤ 0.030), whereas NT5E hypomethylation was associated with decrease...Continue Reading

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Citations

Nov 13, 2019·Biochemical Genetics·Jadwiga GaździckaZofia Ostrowska
Dec 6, 2018·International Journal of Molecular Sciences·Kevin SekPaul A Beavis
Jan 21, 2021·Cancers·Stefania AngelicolaArianna Palladini
Jan 13, 2021·Cancers·Haitang YangSean R R Hall
May 30, 2021·Nature Communications·Lauren GiuffridaPaul A Beavis

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Datasets Mentioned

BETA
GSE87650
GSE71245
GSE38271

Methods Mentioned

BETA
RNA-Seq
RNA

Clinical Trials Mentioned

NCT02655822
NCT02403193
NCT02754141
NCT02503774
NCT03381274
NCT03267589

Software Mentioned

SPSS

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