目的:为了确定基因表达谱(GEP)之间的关联,下一代测序(NGS),黑色素瘤中优先表达的抗原(PRAME)特征,葡萄膜黑色素瘤(UM)患者的转移风险。
方法:自2020年11月至2022年7月,对接受近距离放射治疗或单眼肿瘤科医生摘除的UM患者进行了回顾性分析。临床病理特征,患者结果,GEP分类,NGS,并记录PRAME结果。
结果:综合GEP,PRAME,和NGS测试是在135UMs上进行的。真核翻译起始因子1A的存在,X染色体和剪接因子3B亚基1突变与GEP1A类和GEP1B类显著相关,分别。BRCA相关蛋白1突变的存在与GEP2类显著相关。具有真核翻译起始因子1A的肿瘤的平均最大基底直径,X染色体突变明显小于剪接因子3B亚基1突变和BRCA1相关蛋白1突变。2类肿瘤比GEP1类肿瘤转移更快。与没有驱动突变或根本没有突变的肿瘤相比,具有剪接因子3B亚基1和/或BRCA1相关蛋白1突变的肿瘤转移更快。与具有BRCA1相关蛋白1的肿瘤相比,具有剪接因子3B亚基1的肿瘤转移时间没有显着差异(P值=0.97)。40例肿瘤(30%)PRAME阳性,其余95例肿瘤(70%)为PRAME阴性。与没有PRAME阳性状态的肿瘤相比,具有PRAME阳性状态的肿瘤的转移时间没有显着差异(P值=0.11)。
结论:GEP,NGS,和PRAME表达分析有助于确定UM中不同水平的转移风险。尽管存在其他预后测试,以下研究报告了在UM中使用NGS进行转移性预后。然而,NGS存在局限性,尤其是技术上难以活检的小病灶。
OBJECTIVE: To determine the association between gene-expression profiling (GEP), next-generation sequencing (NGS), preferentially expressed antigen in melanoma (PRAME) features, and metastatic risk in patients with uveal melanoma (UM).
METHODS: A retrospective analysis of patients with UM treated by brachytherapy or enucleation by a single ocular oncologist was conducted from November 2020 and July 2022. Clinicopathologic features, patient outcomes, GEP classification, NGS, and PRAME results were recorded.
RESULTS: Comprehensive GEP, PRAME, and NGS testing was performed on 135 UMs. The presence of eukaryotic translation initiation factor 1A, X-chromosomal and splicing factor 3B subunit 1 mutations was significantly associated with GEP class 1A and GEP class 1B, respectively. The presence of BRCA- associated protein-1 mutation was significantly associated with GEP class 2. The average largest basal diameter for tumors with eukaryotic translation initiation factor 1A, X-chromosomal mutations was significantly smaller than those with splicing factor 3B subunit 1 mutations and BRCA1-associated protein-1 mutations. Class 2 tumors metastasized sooner than GEP class 1 tumors. Tumors with splicing factor 3B subunit 1 and/or BRCA1-associated protein-1 mutations metastasized sooner compared with tumors that had either no driver mutation or no mutations at all. Tumors with splicing factor 3B subunit 1 did not have a significantly different time to metastasis compared with tumors with BRCA1-associated protein-1 (P value = 0.97). Forty tumors (30%) were PRAME positive, and the remaining 95 tumors (70%) were PRAME negative. Tumors with PRAME-positive status did not have a significantly different time to metastasis compared with tumors without PRAME-positive status (P value = 0.11).
CONCLUSIONS: GEP, NGS, and PRAME expression analysis help determine different levels of metastatic risk in UM. Although other prognostic tests exist, the following study reports on the use of NGS for metastatic prognostication in UM. However, limitations of NGS exist, especially with small lesions that are technically difficult to biopsy.