Development of a Prognostic Genetic Signature to Predict the Metastatic Risk Associated with Cutaneous Melanoma
Development of a Prognostic Genetic Signature to Predict the Metastatic Risk Associated with Cutaneous Melanoma
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DOI：
10.1158/1078-0432.ccr-13-3316
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发表时间：
2015-01-01
影响因子：
11.5
通讯作者：
Stone, John F.
中科院分区：
文献类型：
--
作者：
Gerami, Pedram;Cook, Robert W.;Stone, John F.
目的：发展的基因签名的识别高风险的皮肤黑色素瘤肿瘤将提供一个有价值的预后工具与价值的第一和第二阶段的患者谁代表一个显着的异质性组与a3%至55%的疾病进展和死亡的机会5 years from diagnosis. Experimental Design：一个预后28基因签名被确定通过分析微阵列表达数据。原发性皮肤黑色素瘤肿瘤组织通过RT-PCR的签名的表达进行了评估，并进行径向基机器（RBM）建模，以预测转移的风险。结果：皮肤黑色素瘤肿瘤基因表达的RBM分析报告低风险（类1）或高风险（类2）的转移。在原发性皮肤黑色素瘤肿瘤组织的开发（ROC = 0.93）和验证（ROC = 0.91）队列中，转移风险预测具有高准确性。Kaplan-Meier分析表明，预测1级和2级病例的发展集5年无病生存率（DFS）分别为100%和38%（P <0.0001）。预测的1类和2类病例的验证集DFS率分别为97%和31%（P <0.0001）。基因表达谱（GEP），美国癌症联合委员会阶段，Breslow厚度，溃疡，和年龄是转移风险的独立预测因子根据考克斯回归analysis.Conclusions：GEP签名准确预测转移风险的原发性皮肤黑色素瘤的多中心队列。初步的考克斯回归分析表明，签名是一个独立的预测转移风险的队列。(C)2015年AACR。
Purpose: The development of a genetic signature for the identification of high-risk cutaneous melanoma tumors would provide a valuable prognostic tool with value for stage I and II patients who represent a remarkably heterogeneous group with a3% to 55% chance of disease progression and death 5 years from diagnosis.Experimental Design: A prognostic 28-gene signature was identified by analysis of microarray expression data. Primary cutaneous melanoma tumor tissue was evaluated by RT-PCR for expression of the signature, and radial basis machine (RBM) modeling was performed to predict risk of metastasis.Results: RBM analysis of cutaneous melanoma tumor gene expression reports low risk (class 1) or high risk (class 2) of metastasis. Metastatic risk was predicted with high accuracy in development (ROC = 0.93) and validation (ROC = 0.91) cohorts of primary cutaneous melanoma tumor tissue. Kaplan-Meier analysis indicated that the 5-year disease-free survival (DFS) rates in the development set were 100% and 38% for predicted classes 1 and 2 cases, respectively (P < 0.0001). DFS rates for the validation set were 97% and 31% for predicted classes 1 and 2 cases, respectively (P < 0.0001). Gene expression profile (GEP), American Joint Committee on Cancer stage, Breslow thickness, ulceration, and age were independent predictors of metastatic risk according to Cox regression analysis.Conclusions: The GEP signature accurately predicts metastasis risk in a multicenter cohort of primary cutaneous melanoma tumors. Preliminary Cox regression analysis indicates that the signature is an independent predictor of metastasis risk in the cohort presented. (C) 2015 AACR.