目的：利用生物信息学方法分析与葡萄膜恶性黑色素瘤转移相关的非编码RNA，以及它们作为竞争性内源RNA的作用机制。方法：从癌症基因组图谱(The Cancer Genome Atlas，TCGA)数据库下载80例葡萄膜恶性黑色素瘤患者的RNA测序数据和临床资料，采用edgeR算法分析转移与非转移患者组织中差异表达(differentially expressed，DE)的长链非编码RNA(lncRNA)、微小RNA(miR)和mRNA，并构建lncRNA-miR-mRNA的竞争性内源RNA(competing endogenous RNA，ceRNA)调控网络，基因富集分析和通路分析研究网络中mRNA的生物学功能。Kaplan-Meier生存曲线分析ceRNA网络中核心RNA与生存率的关系。结果：从发生远处转移的葡萄膜恶性黑色素瘤样本中，共鉴定出346个上调的mRNA，118个下调的miR和45个上调的lncRNA。其中67个mRNA，7个miR和30个lncRNA相互组合形成616个ceRNA单元，并形成了一个具有181条边线ceRNA网络。基因富集分析表明：网络中的mRNA富集在肿瘤生成和转移相关的几个基因本体(Gene Ontology)和信号通路。拓扑分析确定了6个核心lncRNA(LINC00861、LINC02421、BHLHE40-AS1、LINC01252、LINC00513和LINC02389)和3个核心mRNA(UNC5D、BCL11B和MTDH)。 所有核心lncRNA、核心mRNA的表达水平和5个miR(miR-221、miR-222、miR-506、miR-507、miR-876)的表达水平均与总体生存率显着相关(均P<0.05)。结论：本研究揭示了几种lncRNA及其相关的ceRNA网络在葡萄膜恶性黑色素瘤转移中的作用，为进一步研究葡萄膜恶性黑色素瘤的发生和/或转移提供了新的方向。

Objective: To elucidate the expression of long non-coding RNAs (lncRNAs) and their roles as competing endogenous RNAs (ceRNAs) in uveal melanoma (UM) metastasis. Methods: RNA sequencing data and clinical information of 80 patients with UM were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed (DE) mRNAs, microRNAs (miR), and lncRNAs between metastatic and non-metastatic individuals with UM were screened using the edgeR algorithm. Gene enrichment analysis was conducted for the DE mRNAs. LncRNA-miR-mRNA regulatory triples and a ceRNA network were constructed. Betweenness centrality was used to screen hub genes and lncRNAs for subnetwork analysis. Kaplan-Meier survival analysis was conducted to explore correlations between the expression of hub RNAs and overall survival in the TCGA UM cohort. Results: A total of 346 upregulated mRNAs, 118 downregulated miRs, and 45 upregulated lncRNAs were identified in samples with systemic metastasis. Among them, 67 mRNAs, 7 miRs, and 30 lncRNAs mapped to 616 ceRNA triples, thus forming an interconnected ceRNA network with 181 edges. Gene enrichment analysis revealed that mRNAs in the network were enriched in multiple gene ontology terms and pathways associated with carcinogenesis and metastasis. Topological analysis identified 6 hub lncRNAs (LINC00861, LINC02421, BHLHE40-AS1, LINC01252, LINC00513, and LINC02389) and 3 hub mRNAs (UNC5D, BCL11B, and MTDH). The expression levels of all hub genes and 5 DEmiRs (miR-221, miR-222, miR-506, miR-507, miR-876) were significantly associated with the overall survival probability. Conclusion: This bioinformatic study revealed the functions of several lncRNAs and their associated ceRNA network in UM metastasis. It provides a novel in silicon evidence for future experimental study on the pathogenesis of systemic metastasis in uveal melanoma, especially from the perspective of non-coding RNA.

目的：探究T盒转录因子2(T-box transcription factor 2,TBX2)在葡萄膜黑色素瘤(uveal melanoma,UVM)中的表达水平、生存预后、免疫浸润相关性。方法：首先通过TIMER2.0数据库分析正常组织和肿瘤组织中TBX2表达和临床特征，从UCSC Xena数据库下载泛癌的生存数据，使用Cox比例风险模型和Kaplan-Meier曲线分析评估TBX2对预后的预测价值。然后使用cBioPortal数据库分析人源TBX2突变前后生存改变，通过BloodSpot和TIMER2.0数据库探究TBX2与癌症免疫浸润之间的相关性。癌症单细胞状态图谱和基因集变异分析(gene set variation analysis,GSVA)探究其表达与分子机制的相关性。结果： 15种肿瘤类型的TBX2 mRNA表达水平显著改变，TBX2是肾上腺皮质癌(adrenocortical carcinoma,ACC)、肾乳头状细胞癌(kidney renal papillary cell carcinoma,KIRP)、UVM典型的生存预后标志物。其突变与生存状态无明显相关性，在UVM中T淋巴细胞浸润水平提高导致不良预后风险升高。此外，在UVM中TBX2通路富集至ATP结合盒(ATP-binding cassette transporter,ABC)转运蛋白、DNA修复和损伤。结论：TBX2在UVM的生存和免疫浸润中起着关键作用，将来可能作为一种UVM预后及免疫治疗效果的预测因子。

Objective: To investigate the expression level of T-box transcription factor 2(TBX2) in uveal melanoma (UVM), the correlation between survival prognosis and immune infiltration. Methods: The expression and clinical features of TBX2in normal and tumorwere analyzed by TIMER2.0 database. The survival data of pancarcinoma were downloaded from UCSC Xena database, and the prognotic value of TBX2 was evaluated using Cox proportional risk model and Kaplan-Meier curve analysis. Then cBioPortal database was used to analyze the changes before and after TBX2 mutation survivalin human, and BloodSpot and TIMER2.0 databases were used to explore the correlation between TBX2 and cancer immune infiltration. Cancer single cell status mapping and gene set variation analysis (GSVA) were used to explore the correlation between its expression and molecular mechanisms. Results: The mRNA expression levels of TBX2 were significantly changed in 15 tumor types. TBX2 is adrenocortical carcinoma (ACC) and kidney renal papillary cell carcinoma (Kidney renal papillary cell carcinoma). KIRP and UVM are typical prognostic markers of survival. The mutation had no significant correlation with survival status, and increased T cell infiltration level in UVM led to increased risk of poor prognosis. In addition, the TBX2 pathway is enriched to the ATP-binding cassette transporter (ABC) transporters, DNA repair, and damage in UVM. Conclusion: TBX2 plays a key role in survival and immune invasion of uveal melanoma.and may be used as a predictor of UVM prognosis and immunotherapy effect in the

future.