Hansen Torben Frøstrup, Kjær-Frifeldt Sanne, Morgenthaler Søren, Blondal Thorarinn, Lindebjerg Jan, Jakobsen Anders, Sørensen Flemming Brandt
J Transl Med. 2014 Sep 10;12:254. doi: 10.1186/s12967-014-0254-6.
Angiogenesis plays a pivotal role in malignant tumour growth and the metastatic process. We analysed the prognostic value of two angiogenesis parameters, microRNA-126 (miRNA-126) and microvessel density (MVD), in a population based cohort of patients operated for stage II colon cancer.
A total of 560 patients were included. Analyses were performed on formalin fixed paraffin embedded tissue from the primary tumours. The analysis of miRNA-126 expression was performed by qPCR. Microvessels were visualised by CD105 and quantified in hot spots using a light microscope. The analyses were correlated with recurrence-free cancer specific survival (RF-CSS) and overall survival (OS).
Low miRNA-126 expression was significantly correlated to T4, high malignancy grade, tumour perforation, fixation, and the presence of microsatellite instability. A prognostic impact on OS was detected in the simple analysis favouring patients with high miRNA-126 expression p = 0.03, and borderline significance as to RF-CSS, p = 0.08. The impact on OS demonstrated borderline significance in a following multiple Cox regression analysis, hazard ratio 0.76 (95% confidence interval, 0.58-1.00), p = 0.051. The MVD estimate was not associated with either RF-CSS, p = 0.49, or OS, p = 0.94.
The current population based study of patients operated for stage II colon cancer demonstrated correlations between several prognostic unfavourable characteristics and miRNA-126 and argues for a possible prognostic impact on overall survival. An influence on survival by the MVD estimate was not detected.
血管生成在恶性肿瘤生长和转移过程中起关键作用。我们分析了两个血管生成参数，即微小RNA-126（miRNA-126）和微血管密度（MVD），在一组接受II期结肠癌手术的人群队列中的预后价值。
共纳入560例患者。对原发肿瘤的福尔马林固定石蜡包埋组织进行分析。通过qPCR分析miRNA-126表达。用CD105使微血管可视化，并使用光学显微镜在热点区域进行定量。分析与无复发生存期（RF-CSS）和总生存期（OS）相关。
低miRNA-126表达与T4、高恶性分级、肿瘤穿孔、固定以及微卫星不稳定性的存在显著相关。在单因素分析中检测到对OS有预后影响，有利于miRNA-126高表达的患者，p = 0.03，对RF-CSS有临界显著性，p = 0.08。在随后的多因素Cox回归分析中，对OS的影响显示出临界显著性，风险比为0.76（95%置信区间为0.58 - 1.00），p = 0.051。MVD估计值与RF-CSS（p = 0.49）或OS（p = 0.94）均无关联。
目前这项基于人群的II期结肠癌手术患者研究表明，几个预后不良特征与miRNA-126之间存在相关性，并提示对总生存期可能有预后影响。未检测到MVD估计值对生存的影响。
