Angiogenic miRNAs, the angiopoietin axis and related TIE2-expressing monocytes affect outcomes in cholangiocarcinoma.
Angiogenic miRNAs, the angiopoietin axis and related TIE2-expressing monocytes affect outcomes in cholangiocarcinoma.
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DOI：
10.18632/oncotarget.25699
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发表时间：
2018-07-06
期刊：
影响因子：
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通讯作者：
Schmelzle M
中科院分区：
文献类型：
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作者：
Atanasov G;Dietel C;Feldbrügge L;Benzing C;Krenzien F;Brandl A;Katou S;Schierle K;Robson SC;Splith K;Wiltberger G;Reutzel-Selke A;Jonas S;Pascher A;Bahra M;Pratschke J;Schmelzle M
肿瘤血管生成在表观遗传和蛋白质水平上都受到调节，并且对免疫细胞应答具有潜在影响。然而，胆管癌（CCA）相关的血管生成生物标志物的重要性是未知的。本研究评估了人类CCA样本中血管生成相关microRNA、血管生成素（Angs）和表达Ang-receptor（TIE 2）的单核细胞的表达，以及肝切除术后的预后意义。在肝内CCA（iCC; n = 43）和肝门CCA（HC; n = 45）的冷冻样品中分析血管生成miRNA。在石蜡包埋的iCC切片中检测到Ang-1和Ang-2以及表达TIE 2的单核细胞（TEM）（n = 88）。miRNA表达和TEM、Angs丰度与临床病理特征和生存率相关。miR-126在76.7%的CCA样本中下调，相对高表达与较小的肿瘤和淋巴结转移减少相关。Ang-1高表达与较少的癌性淋巴管炎和较好的组织学分级相关（均p < 0.05）。iCC中TEM的缺失与CA 19 -9水平升高相关。高相对miR-126和低miR-128水平分别与iCC和HC中的存活率改善相关（所有p < 0.05）。高miR-126、低miR-128和TEM是无复发和总生存期的独立预后因素（所有p < 0.05）。这些结果表明，血管生成miRNAs，Angs和TEM在CCA中具有预后价值。除了血管生成miRNA表达谱、Angs和TEM免疫细胞反应之间可能的功能联系外，这些数据作为新的诊断工具具有临床意义。
Tumour angiogenesis is modulated on both an epigenetic and protein level and has potential implications for immune cell responses. However, the importance of related angiogenic biomarkers in cholangiocarcinoma (CCA) is unknown. This study assessed human CCA samples for the expression of angiogenesis-associated microRNAs, angiopoietins (Angs) and monocytes expressing the Ang-receptor, TIE2, with regards to prognostic significance after liver resection. Angiogenic miRNAs were analysed in frozen samples of intrahepatic CCA (iCC; n = 43) and hilar CCA (HC; n = 45). Ang-1 and Ang-2, as well as TIE2-expressing monocytes (TEMs), were detected in paraffin-embedded iCC sections (n = 88). MiRNA expression and the abundance of TEMs and Angs were correlated with clinicopathological characteristics and survival. MiR-126 was downregulated in 76.7% of all CCA samples, with high relative expression associated with smaller tumours and reduced lymph node metastasis. High Ang-1 expression was associated with less lymphangiosis carcinomatosa and better histological grading (all p < 0.05). The absence of TEMs in iCC correlated with elevated CA19-9 levels. High relative miR-126 and low miR-128 levels were associated with improved survival in iCC and HC, respectively (all p < 0.05). High miR-126, low miR-128 and TEMs were independent prognostic factors for recurrence-free and overall survival (all p < 0.05). These results suggest that angiogenic miRNAs, Angs and TEMs are of prognostic value in CCA. In addition to the possible functional links between angiogenic miRNA expression profiles, Angs and immune-cell responses by TEMs, these data have clinical implications as novel diagnostic tools.