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A multi-factorial genetic model for prognostic assessment of high risk melanoma patients receiving adjuvant interferon

Wang, E and Zhao, Y and Monaco, A and Uccellini, L and Kirkwood, JM and Spyropoulou-Vlachou, M and Panelli, MC and Marincola, FM and Gogas, H (2012) A multi-factorial genetic model for prognostic assessment of high risk melanoma patients receiving adjuvant interferon. PLoS ONE, 7 (7).

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Abstract

Purpose: IFNa was the first cytokine to demonstrate anti-tumor activity in advanced melanoma. Despite the ability of high-dose IFNa reducing relapse and mortality by up to 33%, large majority of patients experience side effects and toxicity which outweigh the benefits. The current study attempts to identify genetic markers likely to be associated with benefit from IFN-a2b treatment and predictive for survival. Experimental design: We tested the association of variants in FOXP3 microsatellites, CTLA4 SNPs and HLA genotype in 284 melanoma patients and their association with prognosis and survival of melanoma patients who received IFNa adjuvant therapy. Results: Univariate survival analysis suggested that patients bearing either the DRB1*15 or HLA-Cw7 allele suffered worse OS while patients bearing either HLA-Cw6 or HLA-B44 enjoyed better OS. DRB1*15 positive patients suffered also worse RFS and conversely HLA-Cw6 positive patients had better RFS. Multivariate analysis revealed that a five-marker genotyping signature was prognostic of OS independent of disease stage. In the multivariate Cox regression model, HLA-B38 (p = 0.021), HLA-C15 (p = 0.025), HLA-C3 (p = 0.014), DRB1*15 (p = 0.005) and CT60*G/G (0.081) were significantly associated with OS with risk ratio of 0.097 (95% CI, 0.013-0.709), 0.387 (95% CI, 0.169-0.889), 0.449 (95% CI, 0.237-0.851), 1.948 (95% CI, 1.221-3.109) and 1.484 (95% IC, 0.953-2.312) respectively. Conclusion: These results suggest that gene polymorphisms relevant to a biological occurrence are more likely to be informative when studied in concert to address potential redundant or conflicting functions that may limit each gene individual contribution. The five markers identified here exemplify this concept though prospective validation in independent cohorts is needed.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wang, E
Zhao, Y
Monaco, A
Uccellini, L
Kirkwood, JMkirkwood@pitt.eduKIRKWOOD
Spyropoulou-Vlachou, M
Panelli, MC
Marincola, FM
Gogas, H
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorKaragiannis, Sophia NUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 24 July 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0040805
Refereed: Yes
Other ID: NLM PMC3404079
PubMed Central ID: PMC3404079
PubMed ID: 22911710
Date Deposited: 10 Oct 2012 14:04
Last Modified: 04 Feb 2019 15:56
URI: http://d-scholarship.pitt.edu/id/eprint/15596

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