目的：通过生物信息学方法探寻促进视网膜母细胞瘤发生的关键基因与分子标记。方法：检索Gene Expression Omnibus(GEO)数据库中的视网膜母细胞瘤表达谱芯片对肿瘤组织与正常视网膜组织的差异基因进行GO与KEGG聚类分析，构建蛋白-蛋白相互作用网络并筛选关键节点，利用受试者工作曲线(ROC)评估临床诊断效能。应用qRT-PCR在正常RPE细胞系与视网膜母细胞瘤细胞系中验证枢纽基因的RNA表达情况结果：在视网膜母细胞瘤数据集GSE97508与GSE110811中获得二者差异表达基因的交集共121个，KEGG分析显示差异基因富集于光传导通路、细胞周期与p53通路上，PPI网络筛选并与上述两个数据集中差异最大的30个基因取交集得到MCM6、DTL、UBE2T、TOP2A、NUSAP1、CENPK、RRM2、RLBP1、RHO共9个关键基因。在独立验证数据集GSE24673中确认以上9个基因的表达差异。利用ROC曲线发现UBE2T、RRM2与RHO的AUC≥80%且具有统计学意义(P>0.05)。在视网膜母细胞瘤细胞系中确认UBE2T与RRM2的mRNA水平均显著高于对照ARPE-19细胞系，而RHO的mRNA水平显著低于对照ARPE-19细胞系。结论：本研究筛选发现UBE2T、RRM2与RHO是视网膜母细胞瘤发生的关键基因，可能成为视网膜母细胞瘤的潜在治疗靶点。

AIM: To explore the key genes and molecular markers involved in the retinoblastoma development through bioinformatics.METHODS: The mRNA microarray datasets from the Gene Expression Omnibus(GEO)database were obtained, and the differentially expressed gene(DEG)between retinoblastoma cell lines and normal retinal pigment epithelial(RPE)cell lines were analyzed through gene ontology(GO)and KEGG enrichment analysis. To screen key genes, establish protein-protein interaction(PPI)network, and use receiver operating characteristic(ROC)curve to assess clinical diagnostic efficacy. The RNA expressions of key genes in retinoblastoma cell lines and normal RPE cell lines were compared by qRT-PCR.RESULTS: A total of 121 DEGs were obtained from the retinoblastoma dataset of GSE97508 and GSE110811. KEGG pathway analysis showed that DEG were enriched in phototransduction, cell cycle, and p53 signaling pathways. A total of 9 key genes, including MCM6, DTL, UBE2T, TOP2A, NUSAP1, CENPK, RRM2, RLBP1, and RHO, were obtained from the intersection of PPI network analysis and the top 30 DEG from each dataset. The differentially expressed 9 key genes were verified in GSE24673. ROC analysis showed that the area under the curve(AUC)for UBE2T, RRM2, and RHO was ≥80%, and there was a statistical significance(P>0.05). The mRNA level of UBE2T and RRM2 in retinoblastoma was significantly higher than APRE-19 cell line, while the mRNA level of RHO was significantly lower than that of ARPE-19 cell line.CONCLUSION: UBE2T, RRM2, and RHO may be served as potential molecular markers and potential therapeutic targets for retinoblastoma.

福建省自然科学基金(No.2021J01360); 福建省卫生健康中青年骨干人才培养项目(No.2020GGB003); 福建省卫生健康青年科研课题(No.2020QNA002); 福建医科大学启航基金(No.2019QH1149); 天津市视网膜功能与疾病重点实验室自主与开放课题(No.2021tjswmm003)