血清外泌体源性长链非编码RNA H19在骨肉瘤中的表达及其临床意义

Expression and diagnostic value of serum exosomes-derived long non-coding RNA H19 in osteosarcoma

目的检测骨肉瘤患者血清外泌体长链非编码RNA(LncRNA)H19的表达水平,分析其与患者临床病理参数的关系,探讨其在骨肉瘤诊断中的价值。方法采用实时荧光定量RT-PCR分别检测46例骨肉瘤患者及50例体检健康者血清外泌体LncRNA H19的表达水平;采用ELISA法检测各组血清中基质金属蛋白酶9(MMP-9)、血管内皮生长因子(VEGF)、胰岛素样生长因子2(IGF-2)的表达水平;分析血清外泌体LncRNA H19表达水平与骨肉瘤患者临床病理参数的相关性;绘制ROC曲线,并分析血清外泌体LncRNA H19对骨肉瘤的诊断价值。结果血清外泌体LncRNA H19的表达水平与骨肉瘤患者的病程及是否发生远处转移相关,差异有统计学意义(P均<0.01),而与患者的性别、年龄、居住地及发病部位均无显著相关性(P均>0.05);骨肉瘤患者血清外泌体中LncRNA H19的表达水平显著高于健康人对照组(P<0.01);血清外泌体LncRNA H19诊断骨肉瘤的ROC曲线下面积(AUCROC)为0.881,敏感性为87.2%,特异性为75.6%,均高于其余各单项指标组。结论外泌体高表达的LncRNA H19可能成为骨肉瘤诊断、靶点的个体化治疗及疗效监测的生物学标志物。

Objective To investigate the expression levels of serum exosomal long non-coding RNA(LncRNA)H19 in the patients with osteosarcoma,its relationship with clinicopathological parameters and its value in the diagnosis of osteosarcoma.Methods The expression levels of serum exosomal LncRNA H19 in 46 patients with osteosarcoma and 50 healthy controls were detected by real-time fluorescent quantitative PCR(RT-PCR).The levels of their serum MMP-9,VEGF and IGF-2 were detected by ELISA.The correlation of the levels of serum exosomal LncRNA H19 with clinicopathological parameters of the patients with osteosarcoma was analyzed,and the value of serum exosomal LncRNA H19 in the diagnosis of osteosarcoma was evaluated by the ROC curve.Results The expression levels of serum exosomal LncRNA H19 was significantly correlated with the course of osteosarcoma and the occurrence of distant metastasis(P<0.01),but not with the gender,age,residence and lesion location of the patients(P>0.05).The expression levels of serum exosomal LncRNA H19 in the patients with osteosarcoma were significantly higher than that in healthy controls(P<0.01).The area under the ROC curve(AUCROC),sensitivity and specificity of serum exosomal LncRNA H19 for the diagnosis of osteosarcoma were 0.881,87.2%and 75.6%,respectively,which were higher than those of serum MMP-9,VEGF and IGF-2.Conclusion Serum exosomal LncRNA H19 may be a biomarker for the diagnosis,individualized treatment and therapeutic effict monitoring of osteosarcoma.