Gene Expression Profiling and PRAME Status Versus Tumor-Node-Metastasis Staging for Prognostication in Uveal Melanoma.

Gene Expression Profiling and PRAME Status Versus Tumor-Node-Metastasis Staging for Prognostication in Uveal Melanoma.
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DOI:
10.1016/j.ajo.2018.07.045
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发表时间:
2018-11
影响因子:
4.2
通讯作者:
Harbour JW
Harbour JW
中科院分区:
医学1区
文献类型:
--
作者:
Cai L;Paez-Escamilla M;Walter SD;Tarlan B;Decatur CL;Perez BM;Harbour JW

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比较葡萄膜黑色素瘤(UM)患者基因表达谱(GEP)联合PRAME状态与临床肿瘤淋巴结转移(TNM)分期的预后准确性。回顾性队列研究。该研究包括240例连续的UM患者。使用经验证的15-基因测定法评估肿瘤的GEP状态(1类或2类),并使用定量PCR评估FRAME表达状态。根据美国癌症联合委员会(AJCC)第8版进行TNM分期。统计分析包括单变量和多变量考克斯比例风险模型。转移是主要终点。GEP 1级128例(53.3%),2级112例(46.7%)。157例(65.4%)病例的PRAME状态为阴性,83例(34.6%)病例为阳性。TNM分期Ⅰ期26例(10.8%),Ⅱ A期67例(27.9%),Ⅱ B期50例(20.8%),Ⅲ A期59例(24.6%),Ⅲ B期38例(15.8%)。在中位随访29个月(平均42个月;范围1-195个月)后,59例(24.6%)病例检测到转移性疾病。与转移相关的变量包括(按显著性降序排列):GEP分级(P=1.5 × 10−8)、最大基底肿瘤直径(P=2.5 × 10−6)、PRAME状态(P=2.6 × 10−6)和TNM分期(P=3.7 × 10−6)。优化的3类GEP/PRAME模型(P = 8.6 × 10−14)的预后准确性上级优化的TNM模型(P = 1.3 × 10−5)。在UM中,使用GEP和FRAME的分子预后检测提供了优于TNM分期的上级预后准确性。
To compare the prognostic accuracy of gene expression profiling (GEP) combined with PRAME status versus the clinical Tumor-Node-Metastasis (TNM) staging in patients with uveal melanoma (UM). Retrospective cohort study. The study included 240 consecutive patients with UM. Tumors were assessed for GEP status (Class 1 or Class 2) using a validated 15-gene assay, and FRAME expression status using quantitative PCR. TNM staging was according to the American Joint Committee on Cancer (AJCC) 8th edition. Statistical analysis included univariate and multivariate Cox proportional hazard models. Metastasis was the primary endpoint. GEP was Class 1 in 128 (53.3%) cases, and Class 2 in 112 (46.7%) cases. PRAME status was negative in 157 (65.4%) cases and positive in 83 (34.6%) cases. TNM was stage I in 26 (10.8%) cases, IIA in 67 (27.9%) cases, IIB in 50 (20.8%) cases, IIIA in 59 (24.6%) cases and IIIB in 38 (15.8%) cases. Metastatic disease was detected in 59 (24.6%) cases after median follow-up of 29 months (mean 42 months; range 1–195 months). Variables associated with metastasis included (in order of decreasing significance): GEP class (P=1.5 × 10−8), largest basal tumor diameter (P=2.5 × 10−6), PRAME status (P=2.6 × 10−6), and TNM stage (P=3.7 × 10−6). The prognostic accuracy of an optimized 3-category GEP/PRAME model (P = 8.6 × 10−14) was superior to an optimized TNM model (P = 1.3 × 10−5). In UM, molecular prognostic testing using GEP and FRAME provides prognostic accuracy that is superior to TNM staging.
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