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Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival
Miriam Potrony1, Esther Carreras2, Fernando Aranda2
1Melanoma Unit, Dermatology Department, Hospital Clínic De Barcelona, IDIBAPS, Universitat De Barcelona, Barcelona, Spain.
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.
Insights
Genetic variations in CD5, a T-cell regulator, impact melanoma survival. The Pro224-Ala471 haplotype is linked to improved outcomes, suggesting inherited factors influence melanoma prognosis.
Area of Science:
- Immunogenetics
- Cancer Genomics
- Melanoma Research
Background:
- Malignant melanoma remains a significant health concern despite advances in treatment.
- Individual survival rates vary widely, suggesting a role for inherited factors.
- T-cell effector function regulators, such as CD5, can influence antitumor immune responses and patient outcomes.
Purpose of the Study:
- To investigate the impact of CD5 single nucleotide polymorphisms (SNPs) on survival in melanoma patients.
- To assess the association of specific CD5 SNPs (rs2241002 and rs2229177) and their ancestral haplotype (Pro224-Ala471) with melanoma prognosis.
Main Methods:
- Retrospective analysis of two independent melanoma patient cohorts (Barcelona, N=493; Essen, N=215).
- Genotyping of CD5 SNPs rs2241002 (Pro224Leu) and rs2229177 (Ala471Val).
- Statistical analysis including odds ratios (OR), hazard ratios (HR), and adjusted p-values to assess survival impact.
Main Results:
- The p.Ala471 variant was associated with a better clinical outcome in both cohorts.
- The p.Leu224 variant correlated with increased melanoma-associated mortality.
- The Pro224-Ala471 haplotype in homozygosis significantly improved melanoma survival across the combined patient cohort (HR=0.27, Adj. p=0.005).
Conclusions:
- Genetic variability in immune-related genes, specifically CD5 SNPs, plays a crucial role in determining clinical outcome for melanoma patients.
- The Pro224-Ala471 haplotype may serve as a predictive marker for improved survival in melanoma.
- These findings underscore the importance of considering host genetic factors in melanoma prognosis and treatment strategies.
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