南方医科大学学报

南方医科大学学报 ›› 2018, Vol. 38 ›› Issue (07): 867-.

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尿液中的长链非编码RNA H19可协助诊断早期的急性肠坏死

戴余雷，颜禄斌，樊洁玲，邹齐   

  • 出版日期:2018-07-20 发布日期:2018-07-20

Urinary long non-coding RNA H19 may serve as a biomarker for early diagnosis of acute intestinal necrosis

  • Online:2018-07-20 Published:2018-07-20

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摘要： 目的探索尿液中的长链非编码RNAH19在多种急腹症中对急性肠坏死的鉴别诊断价值。方法收集急性肠坏死患者的 肠坏死组织、坏死组织旁正常小肠组织各51例；同时收集急性肠坏死患者的血清及尿液样本各51例；并收集健康对照者血清、 尿液各51例，其它10种急腹症患者的血清、尿液各35例；同时收集乳腺癌、胃癌、膀胱癌、急性髓性白血病、以及肺癌患者的血 清、尿液样本各10例；随后通过荧光定量PCR技术对各样本中的H19的表达水平进行精确定量检测；使用Mann-Whitney U检 验（两组）或Kruskal-Wallis H检验（两组以上）比较H19在组间表达的差异性，Spearman检验组间的相关性；最后构建受试者工 作特征（ROC）曲线分析血清和尿液H19对急性肠坏死的诊断价值。结果所收集的急性肠坏死的病例中主要为女性患者，占 35例（68.6%）。总体平均发病年龄为74.4岁，主要病因为肠系膜动脉栓塞或栓子形成，占26例（51.0%）。H19在急性肠坏死的 坏死肠组织中比坏死组织旁的正常肠组织表达显著升高11.2倍（P<0.001）。血清、尿液H19在健康对照者、其它10种常见急腹 症、其他5种癌症患者之间的表达差异无统计学意义（P>0.05）。与健康对照者、其它10种常见急腹症、其他5种癌症患者相比， H19在急性肠坏死患者的血清和尿液样本中都显著升高（P<0.001）。同时，H19在急性肠坏死组织、患者的血清、尿液中的表达 均两两显著正相关（P<0.001）。组织与血清H19表达的相关系数为0.974，血清与尿液H19表达的相关系数为0.967，组织与尿 液H19表达的相关系数为0.917。通过ROC曲线分析，血清和尿液H19对急性肠坏死诊断的曲线下面积（AUC）分别为0.951和 0.915，诊断敏感性分别为94%和79.6%，特异性均为100%。结论发生急性肠坏死时，坏死组织内的H19可向血循环和尿液释 放。尿液H19可作为新颖无创的分子标志物协助诊断早期的急性肠坏死。

Abstract: Objective To explore the value of urinary long non-coding RNA (lncRNA) H19 in the differential diagnosis of acute intestinal necrosis against other abdominal emergencies. Methods Surgical specimens of necrotic intestinal tissues, adjacent normal intestinal tissues, and serum and urine samples were collected from 51 patients with acute intestinal necrosis, and analyzed along with the serum and urine samples from 51 healthy controls, patients with 10 different acute abdominal conditions (35 cases for each condition), and patients with breast cancer, gastric cancer, bladder cancer, acute myeloid leukemia, and lung cancer (10 cases for each malignancy). The expression levels of H19 were measured with quantitative PCR in the collected samples. Receiver-operating characteristic (ROC）curves were used to determine the diagnostic value of serum and urine H19 levels for acute intestinal necrosis. Results The 51 patients with acute intestinal necrosis included 35 women and 26 men (mean age of 74.4 years) with arterial thrombosis as the dominant etiology (26 cases). Compared with that in normal intestinal tissues, H19 was significantly overexpressed by 11.2 times in necrotic intestinal tissues (P<0.001). Serum and urine H19 expression levels did not differ significantly among the healthy controls, patients with other acute abdominal conditions and malignancies (P>0.05). Serum and urine H19 levels were significantly up-regulated in patients with acute intestinal necrosis as compared with those in the other subjects included in the analysis (P<0.001). In patients with acute intestinal necrosis, H19 levels in the necrotic intestinal tissue, serum and urine samples were significantly correlated with correlation coefficients of 0.974 (tissue vs serum), 0.967 (serum vs urine), and 0.917 (tissue vs urine). In ROC curve analysis, the areas under curves (AUCs）of serum and urine H19 for diagnosis of acute intestinal necrosis were 0.951 and 0.915, respectively; their diagnostic sensitivities were 94% and 79.6%, respectively, and they both had a diagnostic specificity of 100%. Conclusion In patients with acute intestinal necrosis, H19 is overexpressed in necrotic intestinal tissues, from which it is released into the blood circulation and urine. Urinary H19 may serve as a novel and non-invasive biomarker that assists in early diagnosis of acute intestinal necrosis.