LRRC59基因在尤文肉瘤的表达与意义△

The expression and significance of LRRC59 gene in Ewing sarcoma

摘要:

［目的］ 本研究旨在揭示富含亮氨酸重复序列的蛋白质 59 （leucine-rich repeat-containing protein 59, LRRC59） 在尤文肉瘤中的表达以及对患者预后的影响 。［方法］ 基于从国际癌症基因组联合体 （International Cancer Genome Consortium, IC- GC）数据库获取的 56 例尤文肉瘤样本的基因表达数据和临床信息，采用 Kaplan-Meier 曲线和单多因素 Cox 回归分析探索 LR- RC59 表达与患者预后之间的关系。通过基因本体 （gene ontology, GO） 分析进一步评估 LRRC59 的生物学功能。Connectivity Map （CMap） 分析筛选可能逆转 LRRC59 生物学效应的药物。实时荧光定量多聚核苷酸链式反应 （real-time quantitative poly- merase chain reaction, RT-qPCR）检测尤文肉瘤细胞中 LRRC59 mRNA 的表达水平。［结果］LRRC59 高表达组患者生存时间更短 （P=0.010）。LRRC59 高表达作为独立风险因素预示着尤文肉瘤患者的不良预后（P<0.05）。GO 分析显示 LRRC59 可能参与调控了肿瘤细胞黏着斑和细胞外基质的形成过程。CMap 分析发现芹菜素、喹诺他汀等药物对尤文肉瘤具有潜在治疗效应。RT-qPCR 进一步验证了 LRRC59 在尤文肉瘤细胞中的表达量高于正常细胞 （P<0.001）。［结论］ LRRC59 是尤文肉瘤的独立预后生物标志物，有望为尤文肉瘤提供一个新型治疗靶点。

Abstract:

[Objective] To reveal the expression of leucine-rich repeat-containing protein 59 (LRRC59) in Ewing sarcoma and its effect on the prognosis of the patients. [Methods] Based on Gene expression data and clinical information of 56 Ewing sarcoma samples obtained from the International Cancer Genome Consortium (ICGC) database, Kaplan-Meier curve and univariate and multivariate Cox regression analysis were used to explore the relationship between LRRC59 expression and its prognosis. The biological function of LRRC59 was further evaluated by Gene Ontology (GO) analysis, while Connectivity Map (CMap) analysis was used to screen the drugs that might reverse the bio- logical effects of LRRC59. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of LRRC59 mRNA in Ewing sarcoma cells. [Results] The patients with high expression of LRRC59 survived significantly shorter (P=0.010) . The high expression of LRRC59 proved an independent risk factor predicting poor prognosis in patients with Ewing sarcoma (P＜0.05) . GO analysis showed that LRRC59 might be involved in regulating the formation of tumor cell focal adhesions and extracellular matrix. CMap analysis found that apigenin, quinostatin and other drugs had potential therapeutic effects on Ewing sarcoma. RT-qPCR further verified that the ex- pression of LRRC59 in Ewing sarcoma cells was higher than that in normal cells (P＜0.001) . [Conclusion] LRRC59 is an independent prog- nostic biomarker for Ewing sarcoma, which is expected to provide a novel therapeutic target for Ewing sarcoma.