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  • 孙文惠子,Dhruba Paudel,欧阳一芹,宋思蕊,童晓文,李怀芳,王建军,初磊.缺氧诱导因子1α和血管内皮生长因子在子宫内膜癌中的表达及临床意义[J].第二军医大学学报,2019,40(4):459-463    [点击复制]
  • SUN Wen-hui-zi,Dhruba Paudel,OUYANG Yi-qin,SONG Si-rui,TONG Xiao-wen,LI Huai-fang,WANG Jian-jun,CHU Lei.Expression and clinical significance of hypoxia-inducible factor 1α and vascular endothelial growth factor in endometrial cancer[J].Acad J Sec Mil Med Univ,2019,40(4):459-463   [点击复制]
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缺氧诱导因子1α和血管内皮生长因子在子宫内膜癌中的表达及临床意义
孙文惠子1,DhrubaPaudel1,欧阳一芹2*,宋思蕊2,童晓文2,李怀芳2,王建军2,初磊2
0
(1. 同济大学医学院, 上海 200092;
2. 同济大学附属同济医院妇产科, 上海 200065
*通信作者)
摘要:
目的 分析缺氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)在子宫内膜癌和癌旁组织中的表达差异,探讨缺氧状态以及这2种蛋白在子宫内膜癌发生、发展中的临床意义。方法 选择2011年1月至2012年12月在同济大学附属同济医院接受手术治疗的子宫内膜癌患者128例,采用免疫组织化学法检测术后癌组织和配对癌旁组织中HIF1-α和VEGF蛋白表达,并对患者进行定期随访,分析这2种蛋白表达与患者预后的关系。构建人子宫内膜癌细胞缺氧模型,检测细胞中HIF1-α和VEGF蛋白表达,并观察细胞增殖、侵袭及凋亡情况。结果 子宫内膜癌组织中HIF-1α和VEGF蛋白阳性表达率均高于癌旁组织(P均<0.05),HIF-1α蛋白在淋巴结转移阳性、高组织学分级、肿瘤最大径≥4 cm和孕激素受体阳性的患者中阳性率较高(P均<0.05),VEGF蛋白在淋巴结转移阳性、高组织学分级、肌层浸润较深、肿瘤最大径≥4 cm、雌激素受体阳性、孕激素受体阳性和高病理分期的患者中阳性率较高(P均<0.05);HIF-1α阴性患者的5年总生存率高于阳性患者(P<0.05),VEGF阴性患者5年总生存率与阳性患者相比差异无统计学意义(P>0.05)。人子宫内膜癌细胞缺氧模型中,HIF-1α和VEGF蛋白表达均增加(P均<0.05),细胞增殖和侵袭能力均增强(P均<0.05),凋亡减少(P<0.05)。结论 HIF-1α和VEGF蛋白与子宫内膜癌的发展有关,HIF-1α蛋白表达阳性提示预后不良。
关键词:  子宫内膜肿瘤  缺氧诱导因子1α  血管内皮生长因子类  预后
DOI:10.16781/j.0258-879x.2019.04.0459
投稿时间:2019-01-01修订日期:2019-02-22
基金项目:上海市科学技术委员会科研计划项目(16411950200),中央高校基本科研业务费学科交叉项目(0400219380).
Expression and clinical significance of hypoxia-inducible factor 1α and vascular endothelial growth factor in endometrial cancer
SUN Wen-hui-zi1,Dhruba Paudel1,OUYANG Yi-qin2*,SONG Si-rui2,TONG Xiao-wen2,LI Huai-fang2,WANG Jian-jun2,CHU Lei2
(1. Tongji University School of Medicine, Shanghai 200092, China;
2. Department of Obstetrics and Gynecology, Tongji Hospital of Tongji University, Shanghai 200065, China
*Corresponding author)
Abstract:
Objective To investigate the difference of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression in endometrial cancer and para-carcinoma tissues, and to explore the clinical significance of hypoxia and the two proteins in the development and progression of endometrial cancer. Methods From Jan. 2011 to Dec. 2012, 128 patients with endometrial cancer underwent surgery in Tongji Hospital of Tongji University. The expression of HIF-1α and VEGF in cancer tissues and paired para-carcinoma tissues was detected using immunohistochemical method. The patients were followed up regularly, and the relationship between the expression of HIF-1α and VEGF and the prognosis of the patients was analyzed. The hypoxic cell model of human endometrial cancer was constructed to detect the expression of HIF-1α and VEGF proteins and observe the cell proliferation, invasion and apoptosis. Results The positive rates of HIF-1α and VEGF in cancer tissues were significantly higher than those in the para-carcinoma tissues (both P<0.05). The positive rate of HIF-1α was higher in the patients with lymph node metastasis, high histological grade, maximal tumor dimeter ≥ 4 cm or positive progesterone receptor (all P<0.05). The positive rate of VEGF was higher in the patients with lymph node metastasis, high histological grade, deep myometrial invasion, maximal tumor dimeter ≥ 4 cm, positive estrogen receptor, positive progesterone receptor or high pathological stage (all P<0.05). The 5-year overall survival rate of the patients with negative HIF-1α was significantly higher than that of the patients with positive HIF-1α (P<0.05), while there was no significant difference in the 5-year overall survival rate between the patients with negative and positive VEGF (P>0.05). In the hypoxic cell model of human endometrial cancer, the expression levels of HIF-1α and VEGF were significantly increased, cell proliferation and invasion were significantly increased, and the cell apoptosis was significantly reduced (all P<0.05). Conclusion HIF-1α and VEGF are related to the progress of endometrial cancer, and positive expression of HIF-1α indicates a poor prognosis.
Key words:  endometrial neoplasms  hypoxia-inducible factor 1α  vascular endothelial growth factors  prognosis