食管鳞状细胞癌组织中BTG-1的表达及其对食管鳞状细胞癌细胞株EC9706凋亡的影响
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摘要
目的分析食管鳞状细胞癌组织中B细胞转位基因1(BTG-1)的表达及其对食管鳞状细胞癌细胞株EC9706凋亡的影响。方法选取郑州大学第一附属医院2014年1月～2017年12月存档的164个鳞状细胞癌存档手术或内镜活检蜡块、76个癌旁正常组织手术蜡块作为研究对象,采用免疫组化法、原位杂交检测BTG1蛋白表达并分析其与病理参数的关系;建立BTG-1过量表达细胞株,Anncxin V-FITC/PI双标记流式细胞仪检测人食管鳞状细胞癌细胞株EC9706的凋亡情况。结果食管鳞状细胞癌组织BTG-1蛋白、信使核糖核酸(m RNA)阳性表达率低于癌旁正常组织(χ～2=32.718、55.729,均P<0.001);且有淋巴结转移、TNM分期Ⅲ～Ⅳ期、组织学分级Ⅱ～Ⅲ级标本中BTG-1蛋白、m RNA阳性表达率显著较低(χ～2=29.078、5.970、7.660、31.127、8.624、10.624,均P<0.001);且BTG-1组早期细胞凋亡率显著高于空白对照组(t=15.484,P<0.001)。结论食管鳞状细胞癌组织中BTG1的表达显著低于癌旁正常组织,且其与有无淋巴结转移、TNM分期、组织学分级的关系密切,BTG-1高表达或可促进食管鳞状细胞癌细胞凋亡。
Objective To analyze the expression of B-cell translocation gene 1(BTG-1) in tissue of esophageal squamous cell carcinoma and the effect on apoptosis of esophageal squamous cell carcinoma cell line EC9706. Methods A total of 164 paraffin blocks of squamous cell carcinoma collected through surgery or endoscopic biopsy and 76 adjacent normal tissue surgical blocks were collected from the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2017. The expression of BTG-1 protein and m RNA in the two groups were detected by immunohistochemistry and in situ hybridization, and their relationships with pathological parameters were analyzed. The BTG-1 overexpressing cell line was established, and the apoptosis of human esophageal squamous cell carcinoma cell line EC9706 was detected by Annexin V-FITC/PI double labeling flow cytometry. Results The positive expression rates of BTG-1 protein and messenger ribonucleic acid(m RNA) in esophageal squamous cell carcinoma tissues were significantly lower than those in adjacent normal tissues(χ~2=32.718, 55.729; all P﹤ 0.001). The positive expression rates of BTG-1 protein and m RNA in specimens with lymph node metastasis, at TNM stage Ⅲ-Ⅳ and histological grade Ⅱ-Ⅲ were significantly lower than those without lymph node metastasis, at TNM stage Ⅰ-Ⅱ and of histological grade Ⅰ(χ~2=29.078, 5.970, 7.660, 31.127, 8.624, 10.624; all P﹤0.001). The early apoptosis rate in BTG-1 group was significantly higher than that in blank control group(t = 15.484, P < 0.001). Conclusion The expression of BTG1 in tissues of esophageal squamous cell carcinoma is significantly lower than that in adjacent normal tissues. It is closely related to the presence of lymph node metastasis, TNM stage and histological grade. High expression of BTG-1 may promote the apoptosis of cell of esophageal squamous cell carcinoma.
Objective To analyze the expression of B-cell translocation gene 1(BTG-1) in tissue of esophageal squamous cell carcinoma and the effect on apoptosis of esophageal squamous cell carcinoma cell line EC9706. Methods A total of 164 paraffin blocks of squamous cell carcinoma collected through surgery or endoscopic biopsy and 76 adjacent normal tissue surgical blocks were collected from the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2017. The expression of BTG-1 protein and m RNA in the two groups were detected by immunohistochemistry and in situ hybridization, and their relationships with pathological parameters were analyzed. The BTG-1 overexpressing cell line was established, and the apoptosis of human esophageal squamous cell carcinoma cell line EC9706 was detected by Annexin V-FITC/PI double labeling flow cytometry. Results The positive expression rates of BTG-1 protein and messenger ribonucleic acid(m RNA) in esophageal squamous cell carcinoma tissues were significantly lower than those in adjacent normal tissues(χ~2=32.718, 55.729; all P﹤ 0.001). The positive expression rates of BTG-1 protein and m RNA in specimens with lymph node metastasis, at TNM stage Ⅲ-Ⅳ and histological grade Ⅱ-Ⅲ were significantly lower than those without lymph node metastasis, at TNM stage Ⅰ-Ⅱ and of histological grade Ⅰ(χ~2=29.078, 5.970, 7.660, 31.127, 8.624, 10.624; all P﹤0.001). The early apoptosis rate in BTG-1 group was significantly higher than that in blank control group(t = 15.484, P < 0.001). Conclusion The expression of BTG1 in tissues of esophageal squamous cell carcinoma is significantly lower than that in adjacent normal tissues. It is closely related to the presence of lymph node metastasis, TNM stage and histological grade. High expression of BTG-1 may promote the apoptosis of cell of esophageal squamous cell carcinoma.
引文
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[15]马鹏,冯俊,彭涛.凋亡抑制基因Livin在喉鳞状细胞癌中的表达及与预后的关系[J].成都医学院学报,2017,12(4):439-443.
[16]杨东梅,于红刚.Paxillin在消化系统恶性肿瘤发生发展中的研究进展[J].疑难病杂志,2018,17(4):424-427,432.
[17]刘春涛,姜大磊,张政,等.叉头蛋白M1在食管鳞状上皮异型增生至癌变过程中的表达及其与临床病理的相关性[J].临床和实验医学杂志,2017,16(17):1668-1672.
[18]Micheli L,Ceccarelli M,Farioli-Vecchioli S,et al.Control of the Normal and Pathological Development of Neural Stem and Progenitor Cells by the PC3/Tis21/Btg2 and Btg1 Genes[J].J Cell Physiol,2015,230(12):2881-2890.
[19]Zhu R,Li W,Xu Y,et al.Upregulation of BTG1 enhances the radiation sensitivity of human breast cancer in vitro and in vivo[J].Oncol Rep,2015,34(6):3017-3024.
[20]Nan YH,Wang J,Wang Y,et al.MiR-4295 promotes cell growth in bladder cancer by targeting BTG1[J].Am J Transl Res,2016,8(11):4892-4901.
[21]Lu K,Liu C,Tao T,et al.MicroRNA-19a regulates proliferation and apoptosis of castration-resistant prostate cancer cells by targeting BTG1[J].FEBS Lett,2015,589(13):1485-1490.
[22]冯盼盼,李风鸽,王恒,等.B细胞转位基因-1在胃腺癌组织的表达及临床意义[J].中华实验外科杂志,2016,33(6):1643-1645.
[23]孙国贵,张洁,崔大为,等.BTG1在非小细胞肺癌中的表达及其对肺癌细胞增殖、凋亡和侵袭转移的作用[J].临床肿瘤学杂志,2014,19(11):972-976.
[2]Arnold M,Laversanne M,Brown LM,et al.Predicting the Future Burden of Esophageal Cancer by Histological Subtype:International Trends in Incidence up to 2030[J].Am J Gastroenterol,2017,112(8):176-180.
[3]李朝慧,任本洪,孙雪娇,等.顺铂耐药对食管癌细胞增殖、凋亡、迁移和血管生成的影响[J].中国病理生理杂志,2017,33(1):1-6.
[4]王修身,张羲茜,刘晓,等.食管癌同步放化疗的疗效及预后因素分析[J].中华放射肿瘤学杂志,2017,26(4):400-404.
[5]吕赤,苏琪.结肠癌中BTG3蛋白表达及临床意义[J].临床军医杂志,2016,44(12):1256-1258.
[6]张鹏飞,阴继凯,袁利娟,等.mi R-139通过沉默B细胞转位基因3(BTG3)抑制肝细胞癌细胞的增殖[J].细胞与分子免疫学杂志,2017,33(11):1516-1520.
[7]何洪杰,于景翠.抗增殖家族成员TOB1基因与肿瘤[J].临床肿瘤学杂志,2015,20(3):262-265.
[8]宋琦,蒋冬先,侯英勇.食管鳞状细胞癌的分子生物学研究进展[J].中华病理学杂志,2016,45(3):217-220.
[9]刘涛,李涛.食管癌的手术治疗及非手术治疗研究进展[J].医学综述,2016,22(3):505-507.
[10]张桂芳,孟令新,丁兆军.分子靶向治疗食管癌的研究进展[J].中国医师杂志,2015(z2):226-229.
[11]彭磊.人类ErbB-2转录因子1基因相关信号通路的研究进展[J].肿瘤研究与临床,2016,28(6):422-426.
[12]Bai Y,Qiao L,Xie N,et al.Expression and prognosis analyses of the Tob/BTG antiproliferative(APRO)protein family in human cancers[J].PLoS One,2017,12(9):e0 184 902.
[13]陈静,周中成,刘文斌,等.BTG3在胰腺导管腺癌中的表达及其预后价值[J].中华外科杂志,2017,55(11):863.
[14]贺宇彤,李道娟,梁迪,等.2013年中国食管癌发病和死亡估计[J].中华肿瘤杂志,2017,39(4):315.
[15]马鹏,冯俊,彭涛.凋亡抑制基因Livin在喉鳞状细胞癌中的表达及与预后的关系[J].成都医学院学报,2017,12(4):439-443.
[16]杨东梅,于红刚.Paxillin在消化系统恶性肿瘤发生发展中的研究进展[J].疑难病杂志,2018,17(4):424-427,432.
[17]刘春涛,姜大磊,张政,等.叉头蛋白M1在食管鳞状上皮异型增生至癌变过程中的表达及其与临床病理的相关性[J].临床和实验医学杂志,2017,16(17):1668-1672.
[18]Micheli L,Ceccarelli M,Farioli-Vecchioli S,et al.Control of the Normal and Pathological Development of Neural Stem and Progenitor Cells by the PC3/Tis21/Btg2 and Btg1 Genes[J].J Cell Physiol,2015,230(12):2881-2890.
[19]Zhu R,Li W,Xu Y,et al.Upregulation of BTG1 enhances the radiation sensitivity of human breast cancer in vitro and in vivo[J].Oncol Rep,2015,34(6):3017-3024.
[20]Nan YH,Wang J,Wang Y,et al.MiR-4295 promotes cell growth in bladder cancer by targeting BTG1[J].Am J Transl Res,2016,8(11):4892-4901.
[21]Lu K,Liu C,Tao T,et al.MicroRNA-19a regulates proliferation and apoptosis of castration-resistant prostate cancer cells by targeting BTG1[J].FEBS Lett,2015,589(13):1485-1490.
[22]冯盼盼,李风鸽,王恒,等.B细胞转位基因-1在胃腺癌组织的表达及临床意义[J].中华实验外科杂志,2016,33(6):1643-1645.
[23]孙国贵,张洁,崔大为,等.BTG1在非小细胞肺癌中的表达及其对肺癌细胞增殖、凋亡和侵袭转移的作用[J].临床肿瘤学杂志,2014,19(11):972-976.