Luo Wei, Shao Changqing, Li Na, Zhang Fangjie, Guo Shifang, Duan Zhixi, Zheng Qiping, He Hongbo
Department of Orthopedics, Xiangya Hospital, Central South University 87 Xiangya Road, Changsha, Hunan 410008, P.R. China.
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, P.R. China.
Am J Transl Res. 2015 Jul 15;7(7):1236-45. eCollection 2015.
Epidermal growth factor-like domain 7 gene (EGFL7) encodes an angiogenesis related factor and plays a crucial role in many human cancers. Previous studies have suggestedthat EGFL7 acts as a facilitator for tumor angiogenesis. However, little is known as to its role in osteosarcoma. Our aim was to investigate the expression of EGFL7 and to explore its correlation with the clinicopathological features of osteosarcoma. Tumor tissues from 32 Chinese young patients (below age of 24) with osteosarcoma were collected and subjected to EGFL7 detection by immunohistochemistry. The tissues from 10 patients with osteochondroma were collected and analyzed as controls. The intratumoral microvessel density (MVD) was examined by immunohistochemical staining using CD34 antibody. The results showed that patients with osteosarcoma had higher levels of EGFL7 in the tumor tissues compared to patients with osteochondroma (p<0.001). The expression of EGFL7 was significantly higher in advanced osteosarcoma (Enneking IIB-III) than that in early tumor stage (Enneking IA-IIA) (p<0.01). There is also a significant correlation between increased expression of EGFL7 and the Enneking stage (R = 0.714, p<0.001). Moreover, we detected a higher level of EGFL7 expression in tumor tissues of patients with recurrent or metastatic (bone or lung) osteosarcoma than those without recurrence or metastasis after 3 years' follow-up (p<0.01). There is no detectable difference of EGFL7 expression between tumor tissues from different tumor location and sex. Finally, we showed that high level of EGFL7expression was significantly correlated with high MVD (R = 0.829, p<0.001). In conclusion, our study demonstrates for the first time that there was a tumor grade-dependent up-regulation of EGFL7 in osteosarcoma. Elevated EGFL7 expression correlated with poor clinical outcome: i.e. advanced tumor stage, recurrent and metastatic osteosarcoma. Our findings support EGFL7 as a potential prognostic marker, and may provide novel insights for the diagnostics and therapeutics of osteosarcoma.
表皮生长因子样结构域7基因（EGFL7）编码一种血管生成相关因子，在多种人类癌症中发挥关键作用。以往研究表明，EGFL7是肿瘤血管生成的促进因子。然而，其在骨肉瘤中的作用鲜为人知。我们的目的是研究EGFL7的表达情况，并探讨其与骨肉瘤临床病理特征的相关性。收集了32例中国年轻骨肉瘤患者（年龄在24岁以下）的肿瘤组织，采用免疫组织化学法检测EGFL7。收集10例骨软骨瘤患者的组织作为对照进行分析。使用CD34抗体通过免疫组织化学染色检测瘤内微血管密度（MVD）。结果显示，与骨软骨瘤患者相比，骨肉瘤患者肿瘤组织中EGFL7水平更高（p<0.001）。EGFL7在晚期骨肉瘤（Enneking IIB-III期）中的表达明显高于早期肿瘤阶段（Enneking IA-IIA期）（p<0.01）。EGFL7表达增加与Enneking分期之间也存在显著相关性（R = 0.714，p<0.001）。此外，经过3年随访，我们检测到复发或转移（骨或肺）的骨肉瘤患者肿瘤组织中EGFL7表达水平高于无复发或转移的患者（p<0.01）。不同肿瘤部位和性别的肿瘤组织中EGFL7表达无明显差异。最后，我们发现EGFL7高表达与高MVD显著相关（R = 0.829，p<0.001）。总之，我们的研究首次证明骨肉瘤中存在EGFL7的肿瘤分级依赖性上调。EGFL7表达升高与不良临床结局相关，即晚期肿瘤阶段、复发和转移性骨肉瘤。我们的研究结果支持EGFL7作为一种潜在的预后标志物，并可能为骨肉瘤的诊断和治疗提供新的见解。
