ArticleClinical epigenetics2019
Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 85 citations in OpenAlex.
- CD27 expression is a clinically accessible biomarker for predicting immunotherapy response in melanoma.NPJ precision oncology · 2026Article
- Transcriptome combined with single-cell data to construct a prognostic model for glycosylation-related genes in osteosarcoma.Discover oncology · 2026Article
- Predicting skin melanoma progression via LAG-3, TIGIT and HAVCR2.Functional & integrative genomics · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Tumour-Derived sEVs Promote Triple-Negative Breast Cancer Progression Associated with HAVCR2 Upregulation in Macrophages.Oncology research · 2026Article
- Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025Review
- Article
- In situ and dynamic screening of extracellular vesicles as predictive biomarkers in immune-checkpoint inhibitor therapies.Journal of nanobiotechnology · 2025Article
- "Galectin-9: A double-edged sword in Acute Myeloid Leukemia".Annals of hematology · 2025Review
- DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities.Clinical epigenetics · 2025Review
- Multifaceted roles of Galectins: from carbohydrate binding to targeted cancer therapy.Biomarker research · 2025Review
- MYO1G promoter hypomethylation correlates with its mRNA expression, lymphocyte infiltration, and immunotherapy response in melanoma.Frontiers in oncology · 2025Article
- Single-cell transcriptional atlas of tumor-associated macrophages in breast cancer.Breast cancer research : BCR · 2024Article
- A Multi-Omics Analysis of an Exhausted T Cells' Molecular Signature in Pan-Cancer.Journal of personalized medicine · 2024Article
- Identification of a CpG-based signature coupled with gene expression as prognostic indicators for melanoma: a preliminary study.Scientific reports · 2024Article
- Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma.Frontiers in immunology · 2024Review
- Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma.Scientific reports · 2023Article
- An integrated study to decipher immunosuppressive cellular communication in the PDAC environment.NPJ systems biology and applications · 2023Article
- A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9).Genes & diseases · 2023Review
- Integrated analysis of single-cell and bulk RNA-sequencing reveals the poor prognostic value of ABCA1 in gastric adenocarcinoma.Discover oncology · 2023Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe T cell immunoglobulin and mucin-domain containing-3 receptor TIM-3 (also known as hepatitis A virus cellular receptor 2, encoded by HAVCR2) and its ligand galectin 9 (LGALS9) are promising targets for immune checkpoint inhibition immunotherapies. However, little is known about epigenetic regulation of the encoding genes. This study aimed to investigate the association of TIM-3 and LGALS9 DNA methylation with gene expression, patients' survival, as well as molecular and immune correlates in malignant melanoma.
resultsMethylation of all six TIM-3 CpGs correlated significantly with TIM-3 mRNA levels (P ≤ 0.05). A strong inverse correlation (Spearman's ρ = - 0.49) was found in promoter regions, while a strong positive correlation (ρ = 0.63) was present in the gene body of TIM-3. High TIM-3 mRNA expression (hazard ratio (HR) = 0.88, 95% confidence interval (CI) [0.81-0.97], P = 0.007) was significantly associated with better overall survival. Seven of the eight LGALS9 CpG sites correlated significantly with LGALS9 mRNA levels (P ≤ 0.003). Methylation at five CpG sites showed a strong inverse correlation (Spearman's ρ = - 0.67) and at two sites a weak positive correlation (Spearman's ρ = 0.15). High LGALS9 mRNA expression was significantly associated with increased overall survival (HR = 0.83, 95%CI [0.75-0.93], P = 0.001). In addition, we found significant correlations between TIM-3 and LGALS9 methylation and mRNA expression with immune cell infiltrates and significant differences among distinct immune cell subsets.
conclusionsOur study points toward an epigenetic regulation of TIM-3 and LGALS9 via DNA methylation and might provide an avenue for the development of a predictive biomarker for response to immune checkpoint blockade.
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