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Title: Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival
Author: Potrony, Miriam
Carreras Margalef, Esther
Aranda, Fernando
Zimmer, Lisa
Puig Butillé, Joan Anton
Tell-Marti, Gemma
Armiger, Noelia
Sucker, Antje
Gimenez-Xavier, Pol
Martinez-Florensa, Mario
Carrera Álvarez, Cristina
Malvehy, J. (Josep)
Schadendorf, Dirk
Puig i Sardà, Susana
Lozano Soto, Francisco
Keywords: Melanoma
Receptors cel·lulars
Cell receptors
Issue Date: 15-Sep-2016
Publisher: Wiley
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: International Journal of Cancer, 2016, vol. 139, num. 6, p. 1297-1302
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ISSN: 0020-7136
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (Biomedicina)

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