Liu Yichong, Wang Haiyue, Zhang Qian, Gao Xiaodi, Ji Yiqing, Zhu Yuanzhang, Zhang Jingjing, Luo Wenjuan
Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Clinical Medicine, First College of Clinical Medicine, Binzhou Medical University, Yantai, China.
Front Med (Lausanne). 2024 Dec 2;11:1507576. doi: 10.3389/fmed.2024.1507576. eCollection 2024.
Uveal melanoma (UVM) is an aggressive tumor known for its high metastatic rate, making it necessary to delineate potential molecules that may promote the development of UVM. PLEK2 has been found to promote the progression and metastasis of some tumors, but its role in UVM has not yet been reported. Through this study, we hope to explore the effect of PLEK2 on the prognosis of UVM patients and to discover the potential functional role and intrinsic mechanism of PLEK2.
The GEO datasets GSE211763 and GSE149920 were analyzed using GEO2R to identify differentially expressed genes that may be associated with UVM progression and metastasis. A Protein-Protein Interaction Network (PPI) was constructed to identify key molecules. The correlation between PLEK2 expression and overall survival was evaluated via GEPIA2, and clinical characteristics of UVM patients were compared based on PLEK2 levels. PLEK2 expression in UVM cell lines was assessed using the CCLE database and confirmed by qPCR and western blot. A weighted correlation network analysis (WGCNA) was performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, a search for miRNAs potentially regulating PLEK2 expression was performed using TargetScan, miRWalk, and TarBase databases.
Comparative analysis of the GEO datasets unveiled 79 commonly up-regulated genes and 238 commonly down-regulated genes. The PPI network identified 9 hub genes, with PLEK2 significantly linked to reduced overall survival. Clinical comparisons indicated significant differences in cancer status ( = 0.013) and tumor diameter ( = 0.039) between high and low PLEK2 expression groups. Elevated PLEK2 mRNA levels were confirmed in UVM cell lines compared to retinal pigment epithelial cells. PLEK2 was enriched in the calcium signaling pathway and associated with the Wnt/Ca2+ signaling pathway. A total of 21 miRNAs potentially regulating PLEK2 were predicted.
PLEK2 is upregulated in UVM and correlates with poor patient prognosis, likely influencing the calcium signaling pathway. PLEK2 represents a promising prognostic biomarker and therapeutic target for UVM.
葡萄膜黑色素瘤（UVM）是一种侵袭性肿瘤，以其高转移率而闻名，因此有必要确定可能促进UVM发展的潜在分子。已发现PLEK2可促进某些肿瘤的进展和转移，但其在UVM中的作用尚未见报道。通过本研究，我们希望探讨PLEK2对UVM患者预后的影响，并发现PLEK2的潜在功能作用和内在机制。
使用GEO2R分析GEO数据集GSE211763和GSE149920，以鉴定可能与UVM进展和转移相关的差异表达基因。构建蛋白质-蛋白质相互作用网络（PPI）以识别关键分子。通过GEPIA2评估PLEK2表达与总生存期之间的相关性，并根据PLEK2水平比较UVM患者的临床特征。使用CCLE数据库评估PLEK2在UVM细胞系中的表达，并通过qPCR和蛋白质印迹法进行确认。进行加权基因共表达网络分析（WGCNA），随后进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。最后，使用TargetScan、miRWalk和TarBase数据库搜索可能调节PLEK2表达的miRNA。
对GEO数据集的比较分析揭示了79个常见的上调基因和238个常见的下调基因。PPI网络鉴定出9个枢纽基因，其中PLEK2与总生存期降低显著相关。临床比较表明，高PLEK2表达组和低PLEK2表达组在癌症状态（P = 0.013）和肿瘤直径（P = 0.039）方面存在显著差异。与视网膜色素上皮细胞相比，UVM细胞系中PLEK2 mRNA水平升高得到证实。PLEK2在钙信号通路中富集，并与Wnt/Ca2+信号通路相关。共预测了21个可能调节PLEK2的miRNA。
PLEK2在UVM中上调，与患者预后不良相关，可能影响钙信号通路。PLEK2是UVM一个有前景的预后生物标志物和治疗靶点。
