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骨肉瘤中eIF2α和VEGF的表达及其意义
作者:侯威  张卫  贺洪辉  向亮 
单位:南华大学附属南华医院 关节运动科, 湖南 衡阳 421000
关键词:骨肉瘤 真核翻译起始因子2α 血管内皮生长因子 预后 
分类号:R733.3
出版年·卷·期(页码):2019·38·第五期(774-780)
摘要:

目的:观察骨肉瘤组织中真核翻译起始因子2α(eIF2α)和血管内皮生长因子(VEGF)蛋白及mRNA的表达,探讨其临床意义。方法:收集61例骨肉瘤患者作为研究组1,骨巨细胞瘤患者41例作为对照组1,因外伤切除正常骨组织的患者41例作为正常对照组,均留取术后石蜡包埋组织;收集21例骨肉瘤新鲜组织作为研究组2,21例骨巨细胞瘤新鲜组织作为对照组2。应用免疫组化方法检测研究组1、对照组1和正常对照组中eIF2α和VEGF蛋白的表达,应用蛋白质印迹法检测研究组2和对照组2中eIF2α和VEGF的半定量表达,应用荧光PCR技术检测研究组2和对照组2中eIF2α和VEGF mRNA的表达。结果:免疫组化结果显示,研究组1、对照组1和正常对照组中eIF2α和VEGF表达的阳性率差异有统计学意义(P<0.05)。研究组1中eIF2α和VEGF蛋白的表达均与病变级别、周围组织累犯和肿瘤最大径有关(P<0.05),eIF2α蛋白的表达还与增殖指数有关(P<0.05),VEGF蛋白的表达还与转移有关(P<0.05)。蛋白质印迹法检测结果显示,研究组2和对照组2中eIF2α和VEGF的半定量表达差异有统计学意义(P<0.05)。荧光PCR结果显示,研究组2和对照组2中eIF2α和VEGF mRNA的表达差异有统计学意义(P<0.05)。研究组1中eIF2α蛋白与VEGF蛋白表达呈正相关(r=0.56,P=0.017 0),生存分析显示研究组1中eIF2α和VEGF蛋白的表达与生存时间相关(P<0.05)。结论:骨肉瘤组织中eIF2α和VEGF的蛋白及mRNA表达明显升高,二者呈正相关,共同促进病变的形成和进展。eIF2α和VEGF的表达与预后有关。

Objective: To observe the expressions of eukaryotic translation initiation factor 2α(eIF2α) and vascular endothelial growth factor(VEGF) protein and mRNA in osteosarcoma, explore their correlation and clinical significance. Methods: 61 cases of osteosarcoma were collected as study group1, 41 cases of giant cell tumor of bone were collected as control group1, 41 cases of normal bone tissue(trauma) were collected as normal control group. Paraffin-embedded tissues were retained after operation. 21 cases of fresh osteosarcoma were collected as study group2, 21 cases of giant cell tumor fresh tissue of bone were collected as control group2. Expressions of eIF2α and VEGF protein were detected in study group1, control group1 and normal control group by immunohistochemistry. Semi-quantitative expression of eIF2α and VEGF protein were detected in study group2 and control group2 by Western blotting method. Expression of eIF2α and VEGF mRNA were detected in study group 2 and control group 2 by fluorescent PCR. Results: Immunohistochemical results showed that positive rates of eIF2α and VEGF protein were significantly different in study group1, control group1 and normal control group(P<0.05). In study group1, Expression of eIF2α and VEGF protein were all correlated with pathological grade, surrounding tissue recidivism and tumor maximum diameter, expression of eIF2α protein was also correlated with proliferation index, expression of VEGF protein was also correlated with metastasis. Western blotting results showed that semi-quantitative expression of eIF2α and VEGF were significantly different between study group2 and control group2(P<0.05). Fluorescence PCR results showed that expression of eIF2α and VEGF mRNA were significantly different between study group2 and control group2(P<0.05). There was a positive correlation between eIF2α protein and VEGF protein in study group1. Survival analysis showed that eIF2α and VEGF protein were correlated with survival time in study group1. Conclusion: Expression of eIF2α and VEGF protein and mRNA is significantly higher in osteosarcoma tissues. eIF2α and VEGF are positively correlated. The expression of eIF2α and VEGF is associated with prognosis of osteosarcoma.

参考文献:

[1] 王楠,王璐瑶,杨国辉,等.骨肉瘤组织中血管内皮细胞生长因子、基质金属蛋白酶-2的表达及其临床意义[J].肿瘤基础与临床,2017,30(3):192-194.
[2] KARALI E,BELLOU S,STELLAS D,et al.VEGF Signals through ATF6 and PERK to promote endothelial cell survival and angiogenesis in the absence of ER stress[J].Mol Cell,2014,54(4):559-572.
[3] LIU X,LV Z,ZOU J,et al.Afatinib down-regulates MCL-1 expression through the PERK-eIF2α-ATF4 axis and leads to apoptosis in head and neck squamous cell carcinoma[J].Am J Cancer Res,2016,6(8):1708-1719.
[4] GOLOVKO A,KOJUKHOV A,GUAN B J,et al.The eIF2A knockout mouse[J].Cell Cycle,2016,15(22):3115-3120.
[5] JAMISON S,LIN Y,LIN W.Pancreatic endoplasmic reticulum kinase activation promotes medulloblastoma cell migration and invasion through induction of vascular endothelial growth factor A[J].PLoS One,2015,10(3):e0120252.
[6] 邱恩铎,张晓晶,商冠宁,等.人参皂苷对骨肉瘤患者血清VEGF及TSGF水平的影响及临床疗效[J].现代生物医学进展,2016,16(6):1067-1069.
[7] ZHAO M,SUN L,CHEN S,et al.Borna disease virus infection impacts microRNAs associated with nervous system development,cell differentiation,proliferation and apoptosis in the hippocampi of neonatal rats[J].Mol Med Rep,2015,12(3):3697-3703.
[8] ZHU Z,ZHONG H,ZHOU Q,et al.Inhibition of PKR impairs angiogenesis through a VEGF pathway[J].Am J Physiol Endocrinol Metab,2015,308(6):518-524.
[9] 吴进,刘庆军,曾文容,等.沉默Ether a go-go 1基因调控VEGF/PI3K/AKT抑制骨肉瘤增殖和血管生成的研究[J].肿瘤预防与治疗,2016,29(4):193-198.
[10] INGLIS D J,LAVRANOS T C,BEAUMONT D M,et al.The vascular disrupting agent BNC105 potentiates the efficacy of VEGF and mTOR inhibitors in renal and breast cancer[J].Cancer Biol Ther,2014,15(11):1552-1560.
[11] ZUCAL C,D'AGOSTINO V G,CASINI A,et al.EIF2A-dependent translational arrest protects leukemia cells from the energetic stress induced by NAMPT inhibition[J].Bmc Cancer,2015,15(1):855-856.
[12] CHAKRABORTY S,GHOSH S,BANERJEE B,et al.Mephebrindole,a synthetic indole analog coordinates the crosstalk between p38MAPK and eIF2α/ATF4/CHOP signalling pathways for induction of apoptosis in human breast carcinoma cells[J].Apoptosis,2016,21(10):1-19.
[13] CARRARO V,MAURIN A C,LAMBERT-LANGLAIS S,et al.Amino acid availability controls TRB3 transcription in liver through the GCN2/eIF2α/ATF4 pathway[J].PLoS One,2010,5(12):e15716.
[14] ROSENWALD I B,WANG S,WODA B,et al.Expression of translation initiation factor eIF-2alpha is increased in benign and malignant melanocytic and colonic epithelial neoplasms[J].Cancer,2003,98(5):1080-1088.
[15] BEVILAQUA L R M,CAMMAROTA M.PERK,mTORC1 and eEF2 interplay during long term potentiation:An Editorial for ‘Genetic removal of eIF2a kinase PERK in mice enables hippocampal L-LTP independent of mTORC1 activity’ on page 133[J].J Neurochem,2018,146(2):119-121.
[16] 刘时飞,刘爱东,宋旭东,等.胃腺癌中eIF2α的表达及意义[J].临床与实验病理学杂志,2018,34(6):668-670.
[17] YUAN Y,ZHANG Y,YAO S,et al.The translation initiation factor eIF3i up-regulates vascular endothelial growth factor A,accelerates cell proliferation,and promotes angiogenesis in embryonic development and tumorigenesis[J].J Biol Chem,2014,289(41):28310-28323.
[18] LI Y,FU L,LI J B,et al.Increased expression of EIF5A2,via hypoxia or gene amplification,contributes to metastasis and angiogenesis of esophageal squamous cell carcinoma[J].Gastroenterology,2014,146(7):1701-1713.
[19] 韩力,刘琳.靶向VEGF/VEGFR路径治疗肝细胞癌的临床研究进展[J].东南大学学报(医学版),2017,36(2):266-270.
[20] 苏欢,陈明.炎症反应与肿瘤微环境对前列腺癌作用机制的研究进展[J].东南大学学报(医学版),2017,36(5):847-851.

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