Dataset Information

Prognostic and predictive value of PD-L2 DNA methylation and mRNA expression in melanoma.

ABSTRACT:

Background

PD-L1 (programmed cell death 1 ligand 1) expression in melanoma has been associated with a better response to anti-PD-1 (programmed cell death 1) therapy. However, patients with PD-L1-negative melanomas can respond to anti-PD-1 blockade, suggesting that the other PD-1 ligand, PD-L2 (programmed cell death 1 ligand 2), might also be relevant for efficacy of PD-1 inhibition. We investigated PD-L2 expression and methylation as a prognostic and predictive biomarker in melanoma.

Methods

DNA methylation at five CpG loci and gene expression of PD-L2 were evaluated with regard to survival in 470 melanomas from The Cancer Genome Atlas. PD-L2 promoter methylation in correlation with PD-L2 mRNA and protein expression was analyzed in human melanoma cell lines. Prognostic and predictive value of PD-L2 methylation was validated using quantitative methylation-specific PCR in a multicenter cohort of 129 melanoma patients receiving anti-PD-1 therapy. mRNA sequencing data of 121 melanoma patients receiving anti-PD-1 therapy provided by Liu et al. were analyzed for PD-L2 mRNA expression.

Results

We found significant correlations between PD-L2 methylation and mRNA expression levels in melanoma tissues and cell lines. Interferon-γ inducible PD-L2 protein expression correlated with PD-L2 promoter methylation in melanoma cells. PD-L2 DNA promoter hypomethylation and high mRNA expression were found to be strong predictors of prolonged overall survival. In pre-treatment melanoma samples from patients receiving anti-PD-1 therapy, low PD-L2 DNA methylation and high PD-L2 mRNA expression predicted longer progression-free survival.

Conclusion

PD-L2 expression seems to be regulated via DNA promoter methylation. PD-L2 DNA methylation and mRNA expression may predict progression-free survival in melanoma patients receiving anti-PD-1 immunotherapy. Assessment of PD-L2 should be included in further clinical trials with anti-PD-1 antibodies.

SUBMITTER: Hoffmann F

PROVIDER: S-EPMC7318478 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Prognostic and predictive value of PD-L2 DNA methylation and mRNA expression in melanoma.

Hoffmann Friederike F Zarbl Romina R Niebel Dennis D Sirokay Judith J Fröhlich Anne A Posch Christian C Holderried Tobias A W TAW Brossart Peter P Saavedra Gonzalo G Kuster Pia P Strieth Sebastian S Gielen Gerrit H GH Ring Sandra S SS Dietrich Jörn J Pietsch Torsten T Flatz Lukas L Kristiansen Glen G Landsberg Jennifer J Dietrich Dimo D

Clinical epigenetics 20200626 1

<h4>Background</h4>PD-L1 (programmed cell death 1 ligand 1) expression in melanoma has been associated with a better response to anti-PD-1 (programmed cell death 1) therapy. However, patients with PD-L1-negative melanomas can respond to anti-PD-1 blockade, suggesting that the other PD-1 ligand, PD-L2 (programmed cell death 1 ligand 2), might also be relevant for efficacy of PD-1 inhibition. We investigated PD-L2 expression and methylation as a prognostic and predictive biomarker in melanoma.<h4> ...[more]

PMID: 32586358

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Dataset Information

Prognostic and predictive value of PD-L2 DNA methylation and mRNA expression in melanoma.

Background

Methods

Results

Conclusion

Publications

Prognostic and predictive value of PD-L2 DNA methylation and mRNA expression in melanoma.

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