Yang Chao, Wang Yun-Liang, Sun Ding, Zhu Xiao-Li, Li Zhi, Ni Cai-Fang
Department of Interventional Radiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of General Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
J Cancer Res Ther. 2018;14(4):867-872. doi: 10.4103/jcrt.JCRT_745_17.
Epidermal growth factor-like domain-containing protein 7 (EGFL7) is an endothelial cell-derived secreted factor that regulates vascular tube formation. In human cancer, the specificity of expression is lost as EGFL7 has been detected in tumor cells, in addition to endothelial cells. This study evaluated the intricate relationship between hypoxia-inducible factor 1-alpha (HIF-1α) and EGFL7 under both hyperoxia and hypoxia states.
In the present study, immunohistochemical staining and ELISA were applied to examine the relative level of EGFL7 in 182 cases of hepatocellular carcinoma (HCC) formalin-fixed and paraffin-embedded tissues and 110 cases of HCC serum samples. Quantitative polymerase chain reaction and Western blotting were applied to verify the correlation between serum EGFL7 level and anoxic microenvironment. Immunohistochemical staining was performed to determine the correlation between EGFL7 and HIF1-α.
The correlations between EGFL7 expression and patients' age, tumor size, gender, N-stage, history of cirrhosis, M-stage, history of hepatitis C, and history of hepatitis B were statistically insignificant (P = 0.28, 0.34, 0.71, 0.15, 0.8, 0.2, 0.052, and 0.14, respectively). High level of EGFL7 was significantly correlated with overall survival as well as disease-free survival in 182 HCC patients (P = 0.0016 and P < 0.001, respectively). The correlations between serum EGFL7 and vascular invasion and extrahepatic metastasis were statistically significant (P < 0.0001). Among the 35 HIF1-α-positive HCC patients, 69% were medium positive and 31% were strong positive. EGFL7 protein expression level was oxygen dependent in HCC line (P < 0.05).
EGFL7 was found to be a potential predictor for HCC survival and metastasis state; EGFL7 may be a promising biomarker and therapeutic target in human HCC.
含表皮生长因子样结构域蛋白7（EGFL7）是一种内皮细胞衍生的分泌因子，可调节血管生成。在人类癌症中，EGFL7除了在内皮细胞中表达外，在肿瘤细胞中也有表达，其表达特异性丧失。本研究评估了在高氧和低氧状态下缺氧诱导因子1α（HIF-1α）与EGFL7之间的复杂关系。
在本研究中，应用免疫组织化学染色和酶联免疫吸附测定法检测182例肝细胞癌（HCC）福尔马林固定石蜡包埋组织及110例HCC血清样本中EGFL7的相对水平。应用定量聚合酶链反应和蛋白质印迹法验证血清EGFL7水平与缺氧微环境之间的相关性。进行免疫组织化学染色以确定EGFL7与HIF1-α之间的相关性。
EGFL7表达与患者年龄、肿瘤大小、性别、N分期、肝硬化病史、M分期、丙型肝炎病史和乙型肝炎病史之间的相关性无统计学意义（P分别为0.28、0.34、0.71、0.15、0.8、0.2、0.052和0.14）。182例HCC患者中，EGFL7高水平与总生存期及无病生存期显著相关（P分别为0.0016和P<0.001）。血清EGFL7与血管侵犯及肝外转移之间的相关性有统计学意义（P<0.0001）。在35例HIF1-α阳性的HCC患者中，69%为中度阳性，31%为强阳性。HCC细胞系中EGFL7蛋白表达水平依赖于氧（P<0.05）。
EGFL7是HCC生存和转移状态的潜在预测指标；EGFL7可能是人类HCC中有前景的生物标志物和治疗靶点。
