Department of Oncology, University Hospital of North Norway, Tromso, Norway.
Cancer. 2011 Jul 15;117(14):3193-200. doi: 10.1002/cncr.25907. Epub 2011 Jan 24.
Angiogenesis is pivotal in tumor development. Vascular endothelial growth factor-A (VEGF-A) is considered one of the most important angiogenic factors, but lately several microRNAs (miRs) have been associated with vascular development. miR-126 has been related to tumor angiogenesis and in the regulation of VEGF-A. The authors aimed to investigate the prognostic impact of miR-126 and its co-expression with VEGF-A in nonsmall cell lung cancer (NSCLC) patients.
Tumor tissue samples from 335 resected stage I to IIIA NSCLC patients were obtained and tissue microarrays (TMAs) were constructed with 4 cores from each tumor specimen. VEGF-A expression was evaluated by immunohistochemistry, and in situ hybridization was used to evaluate the expression of miR-126.
In the total material, miR-126 was a significant negative prognostic factor in both univariate (P = .005) and multivariate analyses (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.2-2.8, P = .01). Stratified by histology, miR-126 was only significant in squamous cell carcinomas (univariate: P < .001; multivariate: HR 3.1, CI 95% 1.7-5.6, P<.001). Stratified by lymph node status, miR-126 was significant only in the lymph node-positive subgroup (univariate: P<.001; multivariate: HR 4.1, CI 95% 2.0-8.4, P < .001). High miR-126 expression correlated significantly with high VEGF-A expression (P = .037). The co-expression of miR-126 and VEGF-A had a significant prognostic impact (P = .002), with 5-year survival rates of 68%, 51%, and 42% for low/low (n = 150), mixed combinations (n = 129), and high/high (n = 35) expression, respectively.
miR-126 is a strong and independent negative prognostic factor in NSCLC, and its prognostic impact appears related primarily to histology and nodal status.
血管生成在肿瘤的发展中起着关键作用。血管内皮生长因子 A（VEGF-A）被认为是最重要的血管生成因子之一，但最近有几种 microRNAs（miRs）与血管发育有关。miR-126 与肿瘤血管生成和 VEGF-A 的调节有关。作者旨在研究 miR-126 及其与非小细胞肺癌（NSCLC）患者 VEGF-A 的共表达对预后的影响。
从 335 例 I 至 IIIA 期 NSCLC 患者切除的肿瘤组织样本中获得组织微阵列（TMA），并在每个肿瘤标本中用 4 个核心构建 TMA。通过免疫组织化学评估 VEGF-A 的表达，通过原位杂交评估 miR-126 的表达。
在总材料中，miR-126 在单因素（P =.005）和多因素分析（危险比 [HR] 1.8，95%置信区间 [CI] 1.2-2.8，P =.01）中均为显著的预后不良因素。按组织学分层，miR-126 仅在鳞状细胞癌中具有显著意义（单因素：P <.001；多因素：HR 3.1，CI 95% 1.7-5.6，P<.001）。按淋巴结状态分层，miR-126 仅在淋巴结阳性亚组中具有显著意义（单因素：P<.001；多因素：HR 4.1，CI 95% 2.0-8.4，P <.001）。高 miR-126 表达与高 VEGF-A 表达显著相关（P =.037）。miR-126 和 VEGF-A 的共表达具有显著的预后影响（P =.002），低/低（n = 150）、混合组合（n = 129）和高/高（n = 35）表达的 5 年生存率分别为 68%、51%和 42%。
miR-126 是非小细胞肺癌中一种强大而独立的预后不良因素，其预后影响似乎主要与组织学和淋巴结状态有关。
