Voigtländer Torsten, Gupta Shashi K, Thum Sabrina, Fendrich Jasmin, Manns Michael P, Lankisch Tim O, Thum Thomas
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center-Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.
PLoS One. 2015 Oct 2;10(10):e0139305. doi: 10.1371/journal.pone.0139305. eCollection 2015.
Patients with primary sclerosing cholangitis (PSC) are at high risk for the development of cholangiocarcinoma (CC). Analysis of micro ribonucleic acid (MiRNA) patterns is an evolving research field in biliary pathophysiology with potential value in diagnosis and therapy. Our aim was to evaluate miRNA patterns in serum and bile of patients with PSC and/or CC.
Serum and bile from consecutive patients with PSC (n = 40 (serum), n = 52 (bile)), CC (n = 31 (serum), n = 19 (bile)) and patients with CC complicating PSC (PSC/CC) (n = 12 (bile)) were analyzed in a cross-sectional study between 2009 and 2012. As additional control serum samples from healthy individuals were analyzed (n = 12). The miRNA levels in serum and bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation.
Serum analysis revealed significant differences for miR-1281 (p = 0.001), miR-126 (p = 0.001), miR-26a (p = 0.001), miR-30b (p = 0.001) and miR-122 (p = 0.034) between patients with PSC and patients with CC. All validated miRNAs were significantly lower in healthy individuals. MiR-412 (p = 0.001), miR-640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) were significantly different between patients with PSC and PSC/CC in bile.
Patients with PSC and/or CC have distinct miRNA profiles in serum and bile. Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.
原发性硬化性胆管炎(PSC)患者发生胆管癌(CC)的风险较高。微小核糖核酸(MiRNA)模式分析是胆管病理生理学中一个不断发展的研究领域,在诊断和治疗方面具有潜在价值。我们的目的是评估PSC和/或CC患者血清和胆汁中的MiRNA模式。
在2009年至2012年的一项横断面研究中,分析了连续的PSC患者(血清n = 40,胆汁n = 52)、CC患者(血清n = 31,胆汁n = 19)以及PSC合并CC(PSC/CC)患者(胆汁n = 12)的血清和胆汁。另外还分析了健康个体的血清样本(n = 12)作为对照。通过全局MiRNA谱分析及随后的MiRNA特异性聚合酶链反应介导的验证来测定血清和胆汁中的MiRNA水平。
血清分析显示,PSC患者和CC患者之间,miR-1281(p = 0.001)、miR-126(p = 0.001)、miR-26a(p = 0.001)、miR-30b(p = 0.001)和miR-122(p = 0.034)存在显著差异。所有经过验证的MiRNA在健康个体中均显著较低。胆汁中,PSC患者和PSC/CC患者之间,miR-412(p = 0.001)、miR-640(p = 0.001)、miR-1537(p = 0.003)和miR-3189(p = 0.001)存在显著差异。
PSC和/或CC患者的血清和胆汁具有独特的MiRNA谱。此外,PSC基础上合并CC的患者胆汁中的MiRNA浓度不同,表明这些MiRNA具有潜在的诊断价值。