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首页> 美国卫生研究院文献>Experimental and Therapeutic Medicine >Overexpression and correlation of HIF-2α VEGFA and EphA2 in residual hepatocellular carcinoma following high-intensity focused ultrasound treatment: Implications for tumor recurrence and progression
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Overexpression and correlation of HIF-2α VEGFA and EphA2 in residual hepatocellular carcinoma following high-intensity focused ultrasound treatment: Implications for tumor recurrence and progression

机译：高强度聚焦超声治疗后残留肝细胞癌中HIF-2αVEGFA和EphA2的过表达及其相关性：对肿瘤复发和进展的意义

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Rapid growth of residual tumors can occur as a result of their recurrence and progression. The present study aimed to investigate the expression of hypoxia inducible factor-2 subunit α (HIF-2α), vascular endothelial growth factor A (VEGFA), erythropoietin-producing hepatocellular A2 (EphA2) and angiogenesis in residual hepatocellular carcinoma (HCC), following treatment with high-intensity focused ultrasound (HIFU) ablation, in order to investigate the association between protein expression and tumor recurrence and growth. Athymic BALB/c (nuu) mice were subcutaneously inoculated with the HCC cell line HepG2, in order to create xenograft tumors. Approximately 30 days post-inoculation, eight mice were treated with HIFU, whereas eight mice received no treatment and acted as the control group. Residual tumor tissues were obtained from the experimental groups after one month. Levels of HIF-2α, VEGFA, EphA2 and cluster of differentiation 31 (CD31) expression was measured by immunohistochemical staining. CD31-positive vascular endothelial cells were counted to calculate microvascular density (MVD), and western blot analysis was performed to determine levels of HIF-2α, VEGFA, and EphA2 protein. It was found that the expression levels of HIF-2α, VEGFA, EphA2, and MVD proteins in residual HCC tissues were significantly higher than in the control group tissues (P<0.05). Tumor MVD was strongly correlated with VEGFA (R=0.957, P<0.01) and EphA2 (R=0.993, P<0.01) protein expression levels. Furthermore, there was a significant positive correlation between HIF-2α and EphA2 expression (R=0.991, P<0.01). The correlation between VEGFA and EphA2 expression was also positive (R=0.985, P<0.01). These data suggest that overexpression of HIF-2α, VEGFA and EphA2 is related to angiogenesis in residual HCC following HIFU ablation, potentially via their association with key mediators of recurrence.
机译：残留肿瘤的复发和进展可能导致其迅速生长。本研究旨在探讨缺氧诱导因子2亚基α（HIF-2α），血管内皮生长因子A（VEGFA），产生促红细胞生成素的肝细胞A2（EphA2）的表达以及残余肝细胞癌（HCC）中血管生成的表达。为了研究蛋白质表达与肿瘤复发和生长之间的关系，采用高强度聚焦超声（HIFU）消融治疗。将无胸腺BALB / c（nu / nu）小鼠皮下接种HCC细胞系HepG2，以产生异种移植肿瘤。接种后约30天，用HIFU治疗了八只小鼠，而没有接受治疗的八只小鼠充当了对照组。一个月后从实验组获得残留的肿瘤组织。通过免疫组织化学染色测量HIF-2α，VEGFA，EphA2和分化簇31（CD31）表达的水平。对CD31阳性血管内皮细胞计数以计算微血管密度（MVD），并进行Western印迹分析以确定HIF-2α，VEGFA和EphA2蛋白的水平。结果发现，残留HCC组织中HIF-2α，VEGFA，EphA2和MVD蛋白的表达水平明显高于对照组（P <0.05）。肿瘤MVD与VEGFA（R = 0.957，P <0.01）和EphA2（R = 0.993，P <0.01）蛋白表达水平密切相关。此外，HIF-2α与EphA2表达之间存在显着正相关（R = 0.991，P <0.01）。 VEGFA与EphA2表达之间也呈正相关（R = 0.985，P <0.01）。这些数据表明，HIF-2α，VEGFA和EphA2的过度表达与HIFU消融后残余HCC中的血管生成有关，这可能是由于它们与复发的关键介质有关。

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