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2016-09-15

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/107169

Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival

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https://doi.org/10.1002/ijc.30184

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Despite the recent progress in treatment options, malignant melanoma remains a deadly disease. Besides therapy, inherited factors might modulate clinical outcome, explaining in part widely varying survival rates. T-cell effector function regulators on antitumor immune responses could also influence survival. CD5, a T-cell receptor inhibitory molecule, contributes to the modulation of antimelanoma immune responses as deduced from genetically modified mouse models. The CD5 SNPs rs2241002 (NM_014207.3:c.671C > T, p.Pro224Leu) and rs2229177 (NM_014207.3:c.1412C > T, p.Ala471Val) constitute an ancestral haplotype (Pro224-Ala471) that confers T-cell hyper-responsiveness and worsens clinical autoimmune outcome. The assessment of these SNPs on survival impact from two melanoma patient cohorts (Barcelona, N = 493 and Essen, N = 215) reveals that p.Ala471 correlates with a better outcome (OR= 0.57, 95% CI = 0.33-0.99, Adj. p = 0.043, in Barcelona OR = 0.63, 95% CI = 0.40-1.01, Adj. p = 0.051, in Essen). While, p.Leu224 was associated with increased melanoma-associated mortality in both cohorts (OR = 1.87, 95% CI = 1.07-3.24, Adj. p = 0.030 in Barcelona and OR = 1.84, 95% CI = 1.04-3.26, Adj. p = 0.037, in Essen). Furthermore survival analyses showed that the Pro224-Ala471 haplotype in homozygosis improved melanoma survival in the entire set of patients (HR = 0.27, 95% CI 0.11-0.67, Adj. p = 0.005). These findings highlight the relevance of genetic variability in immune-related genes for clinical outcome in melanoma.

Matèries

Melanoma, Receptors cel·lulars, Oncologia

Matèries (anglès)

Melanoma, Cell receptors, Oncology

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (Medicina)

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POTRONY MATEU, Míriam, CARRERAS MARGALEF, Esther, ARANDA, Fernando, ZIMMER, Lisa, PUIG BUTILLÉ, Joan anton, TELL MARTÍ, Gemma, ARMIGER BORRÀS, Noelia, SUCKER, Antje, GIMENEZ-XAVIER, Pol, MARTÍNEZ-FLORENSA, Mario, CARRERA ÁLVAREZ, Cristina, MALVEHY, J. (josep), SCHADENDORF, Dirk, PUIG I SARDÀ, Susana, LOZANO SOTO, Francisco. Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival. _International Journal of Cancer_. 2016. Vol. 139, núm. 6, pàgs. 1297-1302. [consulta: 24 de gener de 2026]. ISSN: 0020-7136. [Disponible a: https://hdl.handle.net/2445/107169]

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