Department of Ophthalmology, Yuncheng Central Hospital, Shanxi Medical University, Yuncheng, Shanxi Province, China.
Department of Cardiology, Yuncheng Central Hospital, Shanxi Medical University, Yuncheng, Shanxi Province, China.
BMC Cancer. 2022 Jul 5;22(1):734. doi: 10.1186/s12885-022-09822-8.
Uveal melanoma (UM) is the most common primary intraocular malignancy with a strong tendency to metastasize. The prognosis is poor once metastasis occurs. The treatment remains challenging for metastatic UM, even though our understanding of UM has advanced, mostly because the complexity of the genetic and immunologic background has not been fully explored.
Single-cell sequencing data were acquired from a healthy dataset and three UM datasets. The differentially expressed genes between primary and metastatic UM in The Cancer Genome Atlas (TCGA) data were attributed to specific cell types and explained with functional annotation. The analysis for cell-cell communication was conducted by "CellChat" to understand the cell crosstalk among the cell clusters and to delineate the dysfunctional signaling pathways in metastatic UM. CCK-8, EdU and transwell assays were performed to verify the function of the genes of interest.
We revealed aberrant signaling pathways with distinct functional statuses between primary and metastatic UM by integrating multiple datasets. The crucial signals contributing most to outgoing or incoming signaling of metastasis were identified to uncover the potential targeting genes. The association of these genes with disease risk was estimated based on survival data from TCGA. The key genes associated with proliferation and metastasis were verified.
Conclusively, we discovered the potential key signals for occurrence and metastasis of UM and provided a theoretical basis for potential clinical application.
葡萄膜黑色素瘤（UM）是最常见的原发性眼内恶性肿瘤，具有很强的转移倾向。一旦发生转移，预后很差。尽管我们对 UM 的认识已经有所提高，但转移性 UM 的治疗仍然具有挑战性，主要是因为遗传和免疫背景的复杂性尚未得到充分探索。
从一个健康数据集和三个 UM 数据集获取单细胞测序数据。TCGA 数据中 UM 原发灶和转移灶之间差异表达的基因被归因于特定的细胞类型，并通过功能注释进行解释。通过“CellChat”进行细胞间通讯分析，以了解细胞簇之间的细胞串扰，并描绘转移性 UM 中功能失调的信号通路。通过 CCK-8、EdU 和 Transwell 测定来验证感兴趣基因的功能。
我们通过整合多个数据集，揭示了原发性和转移性 UM 之间具有不同功能状态的异常信号通路。确定了对转移的传出或传入信号贡献最大的关键信号，以揭示潜在的靶向基因。根据 TCGA 的生存数据估计了这些基因与疾病风险的关联。验证了与增殖和转移相关的关键基因。
总之，我们发现了 UM 发生和转移的潜在关键信号，为潜在的临床应用提供了理论依据。
