ArticleClinical epigenetics2020
Prognostic and predictive value of PD-L2 DNA methylation and mRNA expression in melanoma.
Article in Clinical epigenetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- A relative methylation ordering biomarker of lactylation-related genes predicts prognosis and therapeutic response in cutaneous melanoma.Epigenetics · 2026Article
- DNA methylation heterogeneity in complex tumor microenvironment: Quantitative methods, influencing factors, and clinical implications.Genes & diseases · 2026Review
- The role of programmed cell death 1 in autoimmune diseases: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- RAB37 Exerts a Context-Dependent Role in Cutaneous Melanoma Progression by Promoting Tumor Cell Proliferation and Being Associated with Favorable Immune Characteristics.Cancer management and research · 2026Article
- DNA methyltransferase 1 correlates with immune modulation in pancreatic neuroendocrine tumors.Scientific reports · 2025Article
- Article
- Prognostic and immune correlation of IDO1 promoter methylation in breast cancer.Scientific reports · 2024Article
- Identification of SLC22A17 DNA methylation hotspot as a potential biomarker in cutaneous melanoma.Journal of translational medicine · 2024Article
- MET receptor serves as a promising target in melanoma brain metastases.Acta neuropathologica · 2024Article
- Companion diagnostics and predictive biomarkers for PD-1/PD-L1 immune checkpoint inhibitors therapy in malignant melanoma.Frontiers in immunology · 2024Review
- CTLA4 DNA methylation is associated with CTLA-4 expression and predicts response to immunotherapy in head and neck squamous cell carcinoma.Clinical epigenetics · 2023Article
- ICOS DNA methylation regulates melanoma cell-intrinsic ICOS expression, is associated with melanoma differentiation, prognosis, and predicts response to immune checkpoint blockade.Biomarker research · 2023Article
- The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Identification and Validation of Ferroptosis-Related DNA Methylation Signature for Predicting the Prognosis and Guiding the Treatment in Cutaneous Melanoma.International journal of molecular sciences · 2022Article
- Prognostic value of JAK3 promoter methylation and mRNA expression in clear cell renal cell carcinoma.Journal of advanced research · 2022Article
- High IGKC-Expressing Intratumoral Plasma Cells Predict Response to Immune Checkpoint Blockade.International journal of molecular sciences · 2022Article
- DNA methylation regulates TIGIT expression within the melanoma microenvironment, is prognostic for overall survival, and predicts progression-free survival in patients treated with anti-PD-1 immunotherapy.Clinical epigenetics · 2022Article
- Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma.International journal of molecular sciences · 2022Review
- Programmed Cell Death-1 and Its Ligands as Targets for Therapy of Multiple Myeloma Patients.Cancer management and research · 2022Article
- Epigenetics Regulates Antitumor Immunity in Melanoma.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPD-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.
methodsDNA 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.
resultsWe 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.
conclusionPD-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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.