一种与高尔基体相关的特征,用于预测葡萄膜黑色素瘤的预后和评估肿瘤免疫微环境。
A Golgi apparatus-related signature for predicting prognosis and evaluating the tumor immune microenvironment of uveal melanoma.
作者信息
Ge Xian, Ge Fei, Xiao Longqin, Su Anting
机构信息
Jianyang Eye Hospital of Jianhu County, Yan Chen, Jiangsu, China.
出版信息
Medicine (Baltimore). 2025 Jun 20;104(25):e42909. doi: 10.1097/MD.0000000000042909.
Uveal melanoma (UVM), a highly invasive and metastatic primary eye cancer with poor prognosis, contributes significantly to melanoma-related deaths despite being less common. Despite advances in therapy, the mortality rate remains unchanged due to frequent liver metastases and limited effective prognostic biomarkers. This study employed gene expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases to investigate Golgi apparatus-related gene sets (GGRGs) in UVM. Survival analysis, consensus clustering, and principal component analysis were conducted to identify GGRGs associated with patient outcomes. Additionally, tumor microenvironment was assessed using IOBR tools, and a nomogram was constructed based on Cox regression models for predicting survival probabilities. The biological function of carbohydrate sulfotransferase protein family (CHST9) was evaluated by colony formation assay, transwell invasion assay, and wound healing assay. Univariate Cox regression identified 343 GGRGs significantly correlated with UVM prognosis. Consensus clustering revealed 2 distinct subtypes (cluster1 and cluster2) differing significantly in survival, with cluster2 showing more favorable outcomes. Principal component analysis effectively separated these clusters, while Kaplan-Meier curves confirmed their survival disparity. Least Absolute Shrinkage and Selection Operator Cox regression analysis pinpointed a 5-GGRGs-based signature, termed GGRGs-derived index (GGI), composed of lunatic fringe, KDELR3, CHST9, ATP8B3, and ACAN. This GGI stratified UVM cases into High_GGI and Low_GGI groups across multiple datasets, with the Low_GGI group consistently demonstrating significantly improved survival rates compared to the High_GGI group. Notably, the Low_GGI and High_GGI groups exhibited marked differences in clinicopathological characteristics, drug sensitivities, and immune infiltration levels. Ultimately, GGI and age emerged as independent prognostic factors for UVM and were incorporated into a nomogram, which displayed outstanding performance in predicting patient prognosis. Depletion of CHST9 expression dramatically inhibited the proliferative capacity of UVM cells, concurrently suppressing their metastatic activity and invasive properties. GGRGs are promising predictors of UVM prognosis and may inform personalized treatment strategies, contributing to a deeper understanding of the molecular mechanisms driving this aggressive cancer.
葡萄膜黑色素瘤(UVM)是一种侵袭性和转移性很强的原发性眼癌,预后较差,尽管其发病率较低,但在黑色素瘤相关死亡中占很大比例。尽管治疗取得了进展,但由于频繁的肝转移和有效的预后生物标志物有限,死亡率仍然没有变化。本研究利用来自癌症基因组图谱和基因表达综合数据库的基因表达数据,研究UVM中与高尔基体相关的基因集(GGRGs)。进行生存分析、共识聚类和主成分分析,以确定与患者预后相关的GGRGs。此外,使用IOBR工具评估肿瘤微环境,并基于Cox回归模型构建列线图以预测生存概率。通过集落形成试验、Transwell侵袭试验和伤口愈合试验评估碳水化合物磺基转移酶蛋白家族(CHST9)的生物学功能。单变量Cox回归确定了343个与UVM预后显著相关的GGRGs。共识聚类揭示了2种不同的亚型(cluster1和cluster2),其生存率有显著差异,cluster2显示出更有利的结果。主成分分析有效地分离了这些聚类,而Kaplan-Meier曲线证实了它们的生存差异。最小绝对收缩和选择算子Cox回归分析确定了一个基于5个GGRGs 的特征,称为GGRGs衍生指数(GGI),由lunatic fringe、KDELR3、CHST9、ATP8B3和ACAN组成。该GGI在多个数据集中将UVM病例分为高GGI组和低GGI组,与高GGI组相比,低GGI组的生存率始终显著提高。值得注意的是,低GGI组和高GGI组在临床病理特征、药物敏感性和免疫浸润水平上表现出明显差异。最终,GGI和年龄成为UVM的独立预后因素,并被纳入列线图,该列线图在预测患者预后方面表现出色。CHST9表达的缺失显著抑制了UVM细胞的增殖能力,同时抑制了它们的转移活性和侵袭特性。GGRGs是UVM预后的有希望的预测指标,可能为个性化治疗策略提供信息,有助于更深入地了解驱动这种侵袭性癌症的分子机制。