Yong Xi, Kang Tengyao, Li Tingting, Li Sixuan, Hu Xuerui, Yan Xiang, Zhang Fuzhao, Zheng Jianghua, Yang Qin
Vascular Surgery Department of Affiliated Hospital of North Sichuan Medical College.
Hepatobiliary, Pancreatic and Intestinal Research Institute of North Sichuan Medical College.
Ann Med Surg (Lond). 2024 Jan 3;86(2):831-841. doi: 10.1097/MS9.0000000000001585. eCollection 2024 Feb.
Chromosome 3 loss is an independent risk factor for uveal melanoma (UM), but its exact molecular mechanisms remain unclear. This study was designed to investigate the relationship between chromosome 3 loss and molecular alterations at multiple levels to construct a prognostic model.
Forty-four UM cases with chromosome 3 loss (chr3 del group) and 36 UM cases without copy number variation on chromosome 3 (chr3 wt group) were collected from the Cancer Genome Atlas (TCGA). The TCGA dataset was subjected to a univariate Cox regression analysis to identify different expressed genes, and a subsequent random forest algorithm analysis revealed significant changes in different expressed genes, which were used to develop key biomarkers for UM. Following that, the immune cell infiltration analysis and drug sensitivity analyses were carried out. The UM cell line was then utilized to investigate the potential functions of the key biomarker via cell apoptosis, proliferation, cycle assays, WB, and RT-qPCR.
By analyzing the 80 cases data in TCGA, the authors unveiled molecular changes relevant to loss of chromosome 3 in UM as well as their poor survival. In addition, machine learning analysis identified three hub genes (GRIN2A, ACAN, and MMP9) as potential therapeutic targets. The differentially enriched pathways between the two groups were mainly about immune-system activity, and hub genes expression was also highly correlated with immune infiltration levels.
Chromosome 3 loss has considerable clinical significance for UM, and GRIN2A may be useful in diagnosing, treating, and prognosticating the condition.
3号染色体缺失是葡萄膜黑色素瘤（UM）的独立危险因素，但其确切分子机制尚不清楚。本研究旨在探讨3号染色体缺失与多个水平分子改变之间的关系，以构建预后模型。
从癌症基因组图谱（TCGA）中收集44例存在3号染色体缺失的UM病例（chr3 del组）和36例3号染色体无拷贝数变异的UM病例（chr3 wt组）。对TCGA数据集进行单变量Cox回归分析以鉴定差异表达基因，随后的随机森林算法分析揭示了差异表达基因的显著变化，这些变化被用于开发UM的关键生物标志物。在此之后，进行免疫细胞浸润分析和药物敏感性分析。然后利用UM细胞系通过细胞凋亡、增殖、周期检测、蛋白质免疫印迹（WB）和逆转录定量聚合酶链反应（RT-qPCR）来研究关键生物标志物的潜在功能。
通过分析TCGA中的80例病例数据，作者揭示了与UM中3号染色体缺失相关的分子变化及其较差的生存率。此外，机器学习分析确定了三个核心基因（GRIN2A、ACAN和MMP9）作为潜在治疗靶点。两组之间差异富集的通路主要与免疫系统活性有关，核心基因表达也与免疫浸润水平高度相关。
3号染色体缺失对UM具有重要临床意义，GRIN2A可能有助于UM的诊断、治疗和预后评估。
