Xuan Zi-Xue, Zhang Su, Yuan Shou-Jun, Wang Wei, Yu Jia
Department of Pharmacy, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
World J Surg Oncol. 2016 Sep 2;14(1):237. doi: 10.1186/s12957-016-0992-4.
Non-small cell lung cancer (NSCLC) is the most frequent cause of cancer deaths worldwide. The targeted therapy had made important progress in recent years, but few potential predictive biomarkers for prognosis of NSCLC patients were identified. Angiopoietin-2 (Ang-2), a cytokine upregulated in tumor endothelial cells and some tumor cells including NSCLC, is a partial agonist and antagonist of angiopoietin-1 (Ang-1). Ang-1 is another ligand for the tyrosine kinase receptor Tie2; it promotes recruitment of pericytes and smooth muscle cells, stabilizing vascular networks by binding to Tie2. Although many studies mainly considered that Ang-2 correlated with progression and prognosis of NSCLC significantly, there are much conflicting and controversial data. Therefore, we conducted a meta-analysis to assess the relationship between Ang-2 and prognosis, a clinical outcome of NSCLC.
The search was based on major databases from PubMed, Cochrane Library, EMBASE, and CNKI, and 20 eligible publications (range from 2002 to 2015) are included in our meta-analysis with 2011 NSCLC patients in total. These studies illuminated the correlation between the expression of Ang-2 and NSCLC, based on either prognostic factors or clinicopathological features. Pooled calculations were carried out on the odds ratio (OR) and the corresponding 95 % confidence interval (CI) to perform this meta-analysis, and all statistical analyses were carried out by STATA 12.0 and Review Manager 5.3.
According to our results, the expression of Ang-2 in NSCLC tissues was significantly higher than that in normal lung tissues, indicating that Ang-2 over-expression may be a predictive marker (pooled OR = 5.09, corresponding 95 % confidence interval (95 % CI) 3.10-8.36, p = 0.000). In addition, our pooled data showed that Ang-2 expression was positively correlated with tumor stages (pooled OR = 3.58, 95 % CI 2.40-5.35, p = 0.000), differentiation (pooled OR = 0.65, 95 % CI 0.45-0.94, p = 0.02), lymphatic invasion (pooled OR = 3.15, 95 % CI 1.97-5.03, p = 0.000), and poor survival (pooled OR = 1.93, 95 % CI 1.47-2.52, p = 0.000) of NSCLC, but seems to have no significant impact on tumor size (pooled OR = 1.09, 95 % CI 0.59-2.00, p = 0.78).
These results demonstrate that Ang-2 expression significantly correlated with poor prognosis for patients with NSCLC.
非小细胞肺癌（NSCLC）是全球癌症死亡的最常见原因。近年来靶向治疗取得了重要进展，但很少有潜在的NSCLC患者预后预测生物标志物被识别出来。血管生成素-2（Ang-2）是一种在肿瘤内皮细胞和包括NSCLC在内的一些肿瘤细胞中上调的细胞因子，是血管生成素-1（Ang-1）的部分激动剂和拮抗剂。Ang-1是酪氨酸激酶受体Tie2的另一种配体；它促进周细胞和平滑肌细胞的募集，通过与Tie2结合来稳定血管网络。尽管许多研究主要认为Ang-2与NSCLC的进展和预后显著相关，但仍有许多相互矛盾和有争议的数据。因此，我们进行了一项荟萃分析，以评估Ang-2与NSCLC临床结局预后之间的关系。
检索基于PubMed、Cochrane图书馆、EMBASE和中国知网等主要数据库，我们的荟萃分析纳入了20篇符合条件的出版物（时间范围为2002年至2015年），共2011例NSCLC患者。这些研究基于预后因素或临床病理特征阐明了Ang-2表达与NSCLC之间的相关性。对优势比（OR）和相应的95%置信区间（CI）进行汇总计算以进行此荟萃分析，所有统计分析均通过STATA 12.0和RevMan 5.3进行。
根据我们的结果，NSCLC组织中Ang-2的表达明显高于正常肺组织，表明Ang-2过表达可能是一个预测标志物（汇总OR = 5.09，相应的95%置信区间（95%CI）为3.10 - 8.36，p = 0.000）。此外，我们的汇总数据显示，Ang-2表达与NSCLC的肿瘤分期（汇总OR = 3.58，95%CI 2.40 - 5.35，p = 0.000）、分化程度（汇总OR = 0.65，95%CI 0.45 - 0.94，p = 0.02）、淋巴侵袭（汇总OR = 3.15，95%CI 1.97 - 5.03，p = 0.000）及不良生存（汇总OR = 1.93，95%CI 1.47 - 2.52，p = 0.000）呈正相关，但似乎对肿瘤大小没有显著影响（汇总OR = 1.09，95%CI 0.59 - 2.00，p = 0.78）。
这些结果表明，Ang-2表达与NSCLC患者的不良预后显著相关。
