ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 22 citations in OpenAlex.
- Genetic variants associated with clinical characteristics and atopies in eosinophilic esophagitis.The journal of allergy and clinical immunology. Global · 2026Article
- Inherited mitochondrial genetics as a predictor of immune checkpoint inhibition efficacy in melanoma.Nature medicine · 2025Article
- Novel Prognostic Markers for Skin Cutaneous Melanoma.Clinical, cosmetic and investigational dermatology · 2024Article
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- Germline immunomodulatory expression quantitative trait loci (ieQTLs) associated with immune-related toxicity from checkpoint inhibition.European journal of cancer (Oxford, England : 1990) · 2023Article
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- Immune-related risk score: An immune-cell-pair-based prognostic model for cutaneous melanoma.Frontiers in immunology · 2023Article
- Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis.Life (Basel, Switzerland) · 2022Article
- A genome-wide association study of germline variation and melanoma prognosis.Frontiers in oncology · 2022Article
- Transmembrane adaptor protein PAG is a mediator of PD-1 inhibitory signaling in human T cells.Communications biology · 2021Article
- Perspectives in immunotherapy: meeting report from the immunotherapy bridge (December 2nd-3rd, 2020, Italy).Journal of translational medicine · 2021Article
- Perspectives in immunotherapy: meeting report from the "Immunotherapy Bridge" (December 4th-5th, 2019, Naples, Italy).Journal of translational medicine · 2021Article
- Germline genetic host factors as predictive biomarkers in immuno-oncology.Immuno-oncology technology · 2019Review
- Mechanisms of immunogenicity in colorectal cancer.The British journal of surgery · 2019Review
- Immunomodulatory germline variation associated with the development of multiple primary melanoma (MPM).Scientific reports · 2019Article
- Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop.Journal for immunotherapy of cancer · 2019Review
- Baseline antibody profiles predict toxicity in melanoma patients treated with immune checkpoint inhibitors.Journal of translational medicine · 2018Article
- No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival.PloS one · 2017Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe identification of personalized germline markers with biologic relevance for the prediction of cutaneous melanoma prognosis is highly demanded but to date, it has been largely unsuccessful. As melanoma progression is controlled by host immunity, here we present a novel approach interrogating immunoregulatory pathways using the genome-wide maps of expression quantitative trait loci (eQTL) to reveal biologically relevant germline variants modulating cutaneous melanoma outcomes. EXPERIMENTAL
designUsing whole genome eQTL data from a healthy population, we identified 385 variants significantly impacting the expression of 268 immune-relevant genes. The 40 most significant eQTLs were tested in a prospective cohort of 1,221 patients with cutaneous melanoma for their association with overall (OS) and recurrence-free survival using Cox regression models.
resultsWe identified highly significant associations with better melanoma OS for rs6673928, impacting IL19 expression (HR, 0.56; 95% CI, 0.41-0.77; P = 0.0002) and rs6695772, controlling the expression of BATF3 (HR, 1.64; 95% CI, 1.19-2.24; P = 0.0019). Both associations map in the previously suspected melanoma prognostic locus at 1q32. Furthermore, we show that their combined effect on melanoma OS is substantially enhanced reaching the level of clinical applicability (HR, 1.92; 95% CI, 1.43-2.60; P = 2.38e-5).
conclusionsOur unique approach of interrogating lymphocyte-specific eQTLs reveals novel and biologically relevant immunomodulatory eQTL predictors of cutaneous melanoma prognosis that are independent of current histopathologic markers. The significantly enhanced combined effect of identified eQTLs suggests the personalized utilization of both SNPs in a clinical setting, strongly indicating the promise of the proposed design for the discovery of prognostic or risk germline markers in other cancers. Clin Cancer Res; 22(13); 3268-80. ©2016 AACR.
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