食管癌组织中MTA1、SOX2的表达及与预后的关系研究
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摘要
目的探讨肿瘤转移相关因子MTA1、干细胞转录因子SOX2在食管癌组织中的表达、二者的相关性以及与预后之间的相互关系。方法分别采用免疫细胞化学、Real-time PCR、Western blot方法检测来源于我院肿瘤科2002年6月~2005年6月的144例食管癌组织标本中MTA1、SOX2的表达,并结合以上患者10年随访资料分析其表达与临床病理及食管癌预后的关系。结果 144例免疫组化结果显示,MTA1、SOX2均在细胞核中表达。MTA1阴性或弱阳性率、中等阳性率与强阳性率分别为58.34%、27.08%与14.58%;SOX2阴性或弱阳性率、中等阳性率与强阳性率分别为65.28%、22.92%与11.81%。MTA1、SOX2在食管癌组织中的表达与T分级、临床分期有关,与肿瘤患者的总生存期呈负相关。结论肿瘤转移相关因子MTA1、干细胞转录因子SOX2在食管癌组织中均有不同程度的表达,且存在相关性。MTA1、SOX2在食管癌组织中同时存在高表达与预后不良相关。
Objective To study the expression of tumor metastasis related gene MTA1 and stem cell transcription factor SOX2 in esophageal cancer tissue,the correlation of MTA1 and SOX2,as well as the relationship between them and prognosis,and to provide a theoretical basis for clinical early diagnosis and prognosis. Methods The expression of MTA1 and SOX2 were detected with immunocytochemistry,Real-time PCR,Western blot method in 144 samples of esophageal carcinoma tissues. Combined with follow-up data more than10 years,the relationship between the expression of MTA1 and SOX2,the correlation with clinical pathologic features as well as its relationship with prognosis were analyzed. Results The result showed that both MTA1 and SOX2 were expressed in the cell nucleus of esophageal cancer. The negative or weakly positive rate,moderate positive rate and strong positive rate was 58.34%,27.08% and 14.58% respectively in MTA1 expression,and was 65. 28%,22. 92% and 11. 81% respectively in SOX2 expression. The expression of both MTA1 and SOX2 were related to T staging and clinical stage in esophageal cancer tissues,and negative correlated with overall survival span in esophageal cancer cases. Conclusions Tumor metastasis related factors MTA1 and stem cell transcription factor SOX2 were expressed with different degrees in esophageal cancer tissues,and there was correlation between them. The high expression of MTA1 and SOX2 simultaneously in esophageal cancer tissues were associated with poor prognosis.
Objective To study the expression of tumor metastasis related gene MTA1 and stem cell transcription factor SOX2 in esophageal cancer tissue,the correlation of MTA1 and SOX2,as well as the relationship between them and prognosis,and to provide a theoretical basis for clinical early diagnosis and prognosis. Methods The expression of MTA1 and SOX2 were detected with immunocytochemistry,Real-time PCR,Western blot method in 144 samples of esophageal carcinoma tissues. Combined with follow-up data more than10 years,the relationship between the expression of MTA1 and SOX2,the correlation with clinical pathologic features as well as its relationship with prognosis were analyzed. Results The result showed that both MTA1 and SOX2 were expressed in the cell nucleus of esophageal cancer. The negative or weakly positive rate,moderate positive rate and strong positive rate was 58.34%,27.08% and 14.58% respectively in MTA1 expression,and was 65. 28%,22. 92% and 11. 81% respectively in SOX2 expression. The expression of both MTA1 and SOX2 were related to T staging and clinical stage in esophageal cancer tissues,and negative correlated with overall survival span in esophageal cancer cases. Conclusions Tumor metastasis related factors MTA1 and stem cell transcription factor SOX2 were expressed with different degrees in esophageal cancer tissues,and there was correlation between them. The high expression of MTA1 and SOX2 simultaneously in esophageal cancer tissues were associated with poor prognosis.
引文
[1]赖霄晶,郑晓,毛伟敏.食管癌靶向治疗的研究进展[J].肿瘤学杂志,2015,21(02):142-150.
[2]Correction:Identification of Pax5 as a target of MTA1 in B-cell lymphomas[J].Cancer Res,2015,75(12):2580-2581.doi:10.1158/0008-5472.CAN-15-1095.
[3]Alqarni SS,Murthy A,Zhang W,et al.Insight into the architecture of the NuRD complex:structure of the Rb Ap48-MTA1 subcomplex[J].J Biol Chem,2014,289(32):21844-21855.doi:10.1074/jbc.M114.558940.
[4]Boumahdi S,Driessens G,Lapouge G,et al.SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cellcarcinoma[J].Nature,2014,511(7508):246-250.doi:10.1038/nature13305.
[5]Justilien V,Walsh MP,Ali SA,et al.The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma[J].Cancer Cell,2014,25(2):139-151.doi:10.1016/j.ccr.2014.01.008.
[6]杨晶,张中明.MTA1蛋白在Ⅱa期食管癌组织中的表达及意义[J].山东医药,2011,51(15):91-92.
[7]刘涛,张瑜红,郭建极,等.ⅢA期食管癌组织肿瘤转移相关蛋白1表达与预后的相关性[J].广东医学,2014,35(23):3670-3673.
[8]解智慧.干细胞转录调控因子SOX2在食管鳞癌中的表达与临床预后的关系[D].郑州大学,2013.
[9]王晓彦,吴继锋.食管鳞状细胞癌中Sox2和β-catenin的表达及其临床意义[J].中国组织化学与细胞化学杂志,2014,23(2):142-147.
[10]汤夏冰,李蕾,沈晓辉,等.干细胞转录因子SOX2和OCT4在喉癌中的表达及与预后的关系[J].实用医学杂志,2013,29(5):751-753.
[11]徐毅,丁伟基,李文鹏,等.干细胞转录因子SOX2、OCT4在不同分化程度胃癌组织中的表达及其临床意义[J].中国癌症杂志,2015,25(6):416-423.
[12]中华医学会消化内镜学分会;中国抗癌协会肿瘤内镜专业委员会.中国早期食管癌筛查及内镜诊治专家共识意见(2014年,北京)[J].中国实用内科杂志,2015,35(4):320-337.
[13]Vanner RJ,Remke M,Gallo M,et al.Quiescent Sox2(+)cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma[J].Cancer Cell,2014,26(1):33-47.doi:10.1016/j.ccr.2014.05.005.
[14]刘欢,王海娟,李春晓,等.肿瘤转移相关基因1在食管癌细胞上皮间质转化过程中的促进作用[J].中国综合临床,2015,31(6):421-424.
[15]朱琳燕,王争君.食管癌组织肿瘤转移相关基因1表达与临床病理特征及预后的关系[J].中国临床研究,2016,29(4):461-464.
[16]Iijima Y,Seike M,Noro R,et al.Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma[J].Int J Oncol.2015 Feb;46(2):505-12.doi:10.3892/ijo.2014.2742.
[17]Watanabe H,Ma Q,Peng S,et al.SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas[J].J Clin Invest,2014,124(4):1636-1645.doi:10.1172/JCI71545.
[18]Fang L,Zhang L,Wei W,et al.A methylation-phosphorylation switch determines Sox2 stability and function in ESC maintenance or differentiation[J].Mol Cell,2014,55(4):537-551.doi:10.1016/j.molcel.2014.06.018.
[19]刘建平,付茂勇,夏娟,等.MTA1、VEGF-C在食管鳞癌中的表达及与淋巴管生成的关系[J].中国胸心血管外科临床杂志,2016,23(3):268-273.
[20]滕杨(综述),陈公琰(审校).恶性肿瘤中SOX2基因的研究进展[J].实用肿瘤学杂志,2014,28(2):173-176.
[21]纪晓宁,王小杰.基因Sox2与肿瘤的研究进展[J].肿瘤防治研究,2014,41(12):1352-1356.
[22]Nagaraj SR,Shilpa P,Rachaiah K,et al.Crosstalk between VEGF and MTA1 signaling pathways contribute to aggressiveness of breast carcinoma[J].Mol Carcinog,2015,54(5):333-350.doi:10.1002/mc.22104.
[23]Zhang J.Correlation of MTA1 and prognosis in colon cancer tissues[J].Oncology Progress,2012,52(7):373-380.
[24]Zhou N,Wang H,Liu H,et al.MTA1-upregulated Ep CAM is associated with metastatic behaviors and poor prognosis in lung cancer[J].J Exp Clin Cancer Res,2015,34:157.doi:10.1186/s13046-015-0263-1.
[25]王世东,陈祖华.食管癌的全基因组关联研究进展[J].肿瘤学杂志,2015,21(11):922-927.
[26]杨晨晨(综述),卢晓梅(审校).食管癌与微小RNA关系研究进展[J].新疆医科大学学报,2015(12):1476-1478.
[2]Correction:Identification of Pax5 as a target of MTA1 in B-cell lymphomas[J].Cancer Res,2015,75(12):2580-2581.doi:10.1158/0008-5472.CAN-15-1095.
[3]Alqarni SS,Murthy A,Zhang W,et al.Insight into the architecture of the NuRD complex:structure of the Rb Ap48-MTA1 subcomplex[J].J Biol Chem,2014,289(32):21844-21855.doi:10.1074/jbc.M114.558940.
[4]Boumahdi S,Driessens G,Lapouge G,et al.SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cellcarcinoma[J].Nature,2014,511(7508):246-250.doi:10.1038/nature13305.
[5]Justilien V,Walsh MP,Ali SA,et al.The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma[J].Cancer Cell,2014,25(2):139-151.doi:10.1016/j.ccr.2014.01.008.
[6]杨晶,张中明.MTA1蛋白在Ⅱa期食管癌组织中的表达及意义[J].山东医药,2011,51(15):91-92.
[7]刘涛,张瑜红,郭建极,等.ⅢA期食管癌组织肿瘤转移相关蛋白1表达与预后的相关性[J].广东医学,2014,35(23):3670-3673.
[8]解智慧.干细胞转录调控因子SOX2在食管鳞癌中的表达与临床预后的关系[D].郑州大学,2013.
[9]王晓彦,吴继锋.食管鳞状细胞癌中Sox2和β-catenin的表达及其临床意义[J].中国组织化学与细胞化学杂志,2014,23(2):142-147.
[10]汤夏冰,李蕾,沈晓辉,等.干细胞转录因子SOX2和OCT4在喉癌中的表达及与预后的关系[J].实用医学杂志,2013,29(5):751-753.
[11]徐毅,丁伟基,李文鹏,等.干细胞转录因子SOX2、OCT4在不同分化程度胃癌组织中的表达及其临床意义[J].中国癌症杂志,2015,25(6):416-423.
[12]中华医学会消化内镜学分会;中国抗癌协会肿瘤内镜专业委员会.中国早期食管癌筛查及内镜诊治专家共识意见(2014年,北京)[J].中国实用内科杂志,2015,35(4):320-337.
[13]Vanner RJ,Remke M,Gallo M,et al.Quiescent Sox2(+)cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma[J].Cancer Cell,2014,26(1):33-47.doi:10.1016/j.ccr.2014.05.005.
[14]刘欢,王海娟,李春晓,等.肿瘤转移相关基因1在食管癌细胞上皮间质转化过程中的促进作用[J].中国综合临床,2015,31(6):421-424.
[15]朱琳燕,王争君.食管癌组织肿瘤转移相关基因1表达与临床病理特征及预后的关系[J].中国临床研究,2016,29(4):461-464.
[16]Iijima Y,Seike M,Noro R,et al.Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma[J].Int J Oncol.2015 Feb;46(2):505-12.doi:10.3892/ijo.2014.2742.
[17]Watanabe H,Ma Q,Peng S,et al.SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas[J].J Clin Invest,2014,124(4):1636-1645.doi:10.1172/JCI71545.
[18]Fang L,Zhang L,Wei W,et al.A methylation-phosphorylation switch determines Sox2 stability and function in ESC maintenance or differentiation[J].Mol Cell,2014,55(4):537-551.doi:10.1016/j.molcel.2014.06.018.
[19]刘建平,付茂勇,夏娟,等.MTA1、VEGF-C在食管鳞癌中的表达及与淋巴管生成的关系[J].中国胸心血管外科临床杂志,2016,23(3):268-273.
[20]滕杨(综述),陈公琰(审校).恶性肿瘤中SOX2基因的研究进展[J].实用肿瘤学杂志,2014,28(2):173-176.
[21]纪晓宁,王小杰.基因Sox2与肿瘤的研究进展[J].肿瘤防治研究,2014,41(12):1352-1356.
[22]Nagaraj SR,Shilpa P,Rachaiah K,et al.Crosstalk between VEGF and MTA1 signaling pathways contribute to aggressiveness of breast carcinoma[J].Mol Carcinog,2015,54(5):333-350.doi:10.1002/mc.22104.
[23]Zhang J.Correlation of MTA1 and prognosis in colon cancer tissues[J].Oncology Progress,2012,52(7):373-380.
[24]Zhou N,Wang H,Liu H,et al.MTA1-upregulated Ep CAM is associated with metastatic behaviors and poor prognosis in lung cancer[J].J Exp Clin Cancer Res,2015,34:157.doi:10.1186/s13046-015-0263-1.
[25]王世东,陈祖华.食管癌的全基因组关联研究进展[J].肿瘤学杂志,2015,21(11):922-927.
[26]杨晨晨(综述),卢晓梅(审校).食管癌与微小RNA关系研究进展[J].新疆医科大学学报,2015(12):1476-1478.