Epigenetic modifications of the immune-checkpoint genes CTLA4 and PDCD1 in non-small cell lung cancer results in increased expression

Clinical Epigenetics
Sebastian MarwitzTorsten Goldmann

Abstract

Targeting checkpoint inhibitors using monoclonal antibodies results in significantly better outcome of cancer patients compared to conventional chemotherapy. However, the current companion diagnostics to predict response is so far suboptimal, since they base on more or less reliable immunohistochemical approaches. In order to overcome these limitations, we analyzed epigenetic modifications of PDCD1 (PD1), CD274 (PD-L1), and CTLA4 in NSCLC tissues from 39 patients. Results were correlated with transcriptome data. Significant differences in the CpG-methylation patterns between tumor tissues and matched controls were observed for CTLA4 and PDCD1 (PD1) showing a decreased methylation of these genes compared to matched tumor-free tissues from the same patients. Results were confirmed by bisulfide sequencing in an independent validation cohort. Hypomethylation also resulted in increased expression of these genes as shown by transcriptome data. These epigenetic pathways as a hallmark of NSCLC might be useful to generate more precise diagnostic approaches in the future.

References

Jan 12, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Shuji OginoEdward Giovannucci
Jun 17, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Sebastian MarwitzOle Ammerpohl
Oct 22, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Torsten GoldmannMartin Reck

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Citations

Dec 12, 2018·Journal of Diabetes Research·Chenyue QianChen Fang
Dec 24, 2018·Therapeutic Advances in Medical Oncology·Federico Pio FabrizioLucia Anna Muscarella
Jan 24, 2020·Journal of Clinical Medicine·Qingyang XiaoIsabel Barragán
May 31, 2018·Journal of Experimental & Clinical Cancer Research : CR·Feng XuChaoliu Dai
Apr 8, 2020·Frontiers in Cell and Developmental Biology·Aleksandra FilipovicJoseph Bolen
Oct 4, 2020·Diabetes & Metabolism·Natalie YoussefAssaad A Eid
Feb 25, 2021·Pharmacogenomics and Personalized Medicine·Juliana Machado-RugoloVera Luiza Capelozzi
Apr 23, 2021·Biologics : Targets & Therapy·Elizabeth R HawkinsAstero Klampatsa
Jun 6, 2021·Journal of Experimental & Clinical Cancer Research : CR·Hao ZhangQuan Cheng
Jun 10, 2021·Therapeutic Advances in Medical Oncology·Anastasios GkountakosEmilio Bria
Jan 10, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Helen X ChenMagdalena Thurin

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