Liu Zibin, Yu Lili, Lai Jian, Zhang Rui
Department of Ophthalmology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Pediatrics, Hangzhou Linping TCM Hospital, Hangzhou, Zhejiang, China.
Medicine (Baltimore). 2024 May 3;103(18):e38021. doi: 10.1097/MD.0000000000038021.
Uveal melanoma (UM) is a rare but aggressive malignant ocular tumor with a high metastatic potential and limited therapeutic options, currently lacking accurate prognostic predictors and effective individualized treatment strategies. Public databases were utilized to analyze the prognostic relevance of programmed cell death-related genes (PCDRGs) in UM transcriptomes and survival data. Consensus clustering and Lasso Cox regression analysis were performed for molecular subtyping and risk feature construction. The PCDRG-derived index (PCDI) was evaluated for its association with clinicopathological features, gene expression, drug sensitivity, and immune infiltration. A total of 369 prognostic PCDRGs were identified, which could cluster UM into 2 molecular subtypes with significant differences in prognosis and clinicopathological characteristics. Furthermore, a risk feature PCDI composed of 11 PCDRGs was constructed, capable of indicating prognosis in UM patients. Additionally, PCDI exhibited correlations with the sensitivity to 25 drugs and the infiltration of various immune cells. Enrichment analysis revealed that PCDI was associated with immune regulation-related biological processes and pathways. Finally, a nomogram for prognostic assessment of UM patients was developed based on PCDI and gender, demonstrating excellent performance. This study elucidated the potential value of PCDRGs in prognostic assessment for UM and developed a corresponding risk feature. However, further basic and clinical studies are warranted to validate the functions and mechanisms of PCDRGs in UM.
葡萄膜黑色素瘤（UM）是一种罕见但侵袭性强的恶性眼肿瘤，具有高转移潜能且治疗选择有限，目前缺乏准确的预后预测指标和有效的个体化治疗策略。利用公共数据库分析程序性细胞死亡相关基因（PCDRGs）在UM转录组和生存数据中的预后相关性。进行共识聚类和Lasso Cox回归分析以进行分子亚型分类和风险特征构建。评估PCDRG衍生指数（PCDI）与临床病理特征、基因表达、药物敏感性和免疫浸润的关联。共鉴定出369个预后PCDRGs，其可将UM分为2种分子亚型，预后和临床病理特征存在显著差异。此外，构建了由11个PCDRGs组成的风险特征PCDI，能够指示UM患者的预后。此外，PCDI与25种药物的敏感性以及各种免疫细胞的浸润相关。富集分析显示PCDI与免疫调节相关的生物学过程和途径有关。最后，基于PCDI和性别开发了UM患者预后评估的列线图，表现出优异的性能。本研究阐明了PCDRGs在UM预后评估中的潜在价值，并开发了相应的风险特征。然而，需要进一步的基础和临床研究来验证PCDRGs在UM中的功能和机制。
