Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival.

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.

SUBMITTER: Potrony M 

PROVIDER: S-EPMC5503133 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature