Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.
School of Medicine, Baylor College of Medicine, Houston, Texas.
Retina. 2024 Sep 1;44(9):1580-1589. doi: 10.1097/IAE.0000000000004153.
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).
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.
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).
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.
确定基因表达谱（GEP）、下一代测序（NGS）、黑色素瘤优先表达抗原（PRAME）特征与眼葡萄膜黑色素瘤（UM）患者转移风险之间的关联。
对 2020 年 11 月至 2022 年 7 月期间由同一位眼科肿瘤学家行近距离放射治疗或眼球摘除术治疗的 UM 患者进行回顾性分析。记录临床病理特征、患者结局、GEP 分类、NGS 和 PRAME 结果。
对 135 例 UM 进行了全面的 GEP、PRAME 和 NGS 检测。真核翻译起始因子 1A、X 染色体和剪接因子 3B 亚基 1 突变的存在与 GEP 1A 类和 GEP 1B 类分别显著相关。BRCA 相关蛋白 1 突变的存在与 GEP 2 类显著相关。真核翻译起始因子 1A、X 染色体突变的肿瘤的平均最大基底直径明显小于剪接因子 3B 亚基 1 突变和 BRCA1 相关蛋白 1 突变的肿瘤。2 类肿瘤比 GEP 1 类肿瘤转移得更早。与无驱动突变或无突变的肿瘤相比，具有剪接因子 3B 亚基 1 和/或 BRCA1 相关蛋白 1 突变的肿瘤转移得更早。具有剪接因子 3B 亚基 1 的肿瘤与具有 BRCA1 相关蛋白 1 的肿瘤相比，转移时间没有显著差异（P 值=0.97）。40 例（30%）肿瘤为 PRAME 阳性，其余 95 例（70%）肿瘤为 PRAME 阴性。PRAME 阳性状态的肿瘤与无 PRAME 阳性状态的肿瘤相比，转移时间没有显著差异（P 值=0.11）。
GEP、NGS 和 PRAME 表达分析有助于确定 UM 不同水平的转移风险。尽管存在其他预后检测，但本研究报告了 NGS 在 UM 转移预测中的应用。然而，NGS 存在局限性，尤其是对于技术上难以活检的小病变。
