A multi-factorial genetic model for prognostic assessment of high risk melanoma patients receiving adjuvant interferon.
A multi-factorial genetic model for prognostic assessment of high risk melanoma patients receiving adjuvant interferon.
复制标题
DOI：
10.1371/journal.pone.0040805
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gogas H
中科院分区：
文献类型：
--
作者：
Wang E;Zhao Y;Monaco A;Uccellini L;Kirkwood JM;Spyropoulou-Vlachou M;Panelli MC;Marincola FM;Gogas H
IFNa是第一个在晚期黑色素瘤中表现出抗肿瘤活性的细胞因子。尽管高剂量IFNa能够将复发率和死亡率降低高达33%，但大多数患者都会经历超过益处的副作用和毒性。目前的研究试图确定可能与IFN-a2 b治疗获益相关的遗传标记，并预测生存率。我们在284例黑色素瘤患者中检测了FOXP 3微卫星、CTLA 4 SNP和HLA基因型变异的相关性，以及它们与接受IFNa辅助治疗的黑色素瘤患者的预后和生存的相关性。单因素生存分析显示，携带DRB 1 *15或HLA-Cw 7等位基因的患者OS较差，而携带HLA-Cw 6或HLA-B44等位基因的患者OS较好，DRB 1 *15阳性患者RFS较差，HLA-Cw 6阳性患者RFS较好。多变量分析显示，5个标记物基因分型特征是OS的预后，与疾病分期无关。在多因素考克斯回归模型中，HLA-B38（p = 0.021）、HLA-C15（p = 0.025）、HLA-C3（p = 0.014）、DRB 1 *15（p = 0.005）和CT60*G/G（0.081）与OS显著相关，风险比为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）和1.484（95%IC，0.953-2.312）。这些结果表明，基因多态性相关的生物学事件更有可能是信息时，在音乐会研究，以解决潜在的冗余或冲突的功能，可能会限制每个基因的个人贡献。这里确定的五个标志物证实了这一概念，但需要在独立队列中进行前瞻性验证。
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. 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. 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. 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.
登录
查看更多内容
影响因子：
45.3
作者：
Balch, Charles M.;Gershenwald, Jeffrey E.;Sondak, Vernon K.
通讯作者：
Sondak, Vernon K.
影响因子：
7.4
作者：
Gogas H;Dafni U;Koon H;Spyropoulou-Vlachou M;Metaxas Y;Buchbinder E;Pectasides E;Tsoutsos D;Polyzos A;Stratigos A;Markopoulos C;Panagiotou P;Fountzilas G;Castana O;Skarlos P;Atkins MB;Kirkwood JM
通讯作者：
Kirkwood JM
DOI：
10.1007/s00262-009-0751-2
发表时间：
2010-02
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Bouwhuis MG;Gast A;Figl A;Eggermont AM;Hemminki K;Schadendorf D;Kumar R
通讯作者：
Kumar R
影响因子：
5
作者：
International Multiple Sclerosis Genetics Consortium
通讯作者：
International Multiple Sclerosis Genetics Consortium
影响因子：
45.3
作者：
Kirkwood, JM;Ibrahim, JG;Rao, U
通讯作者：
Rao, U