食管鳞癌患者TP53表达与预后相关性的荟萃分析
|
摘要
目的探讨TP53蛋白阳性表达在食管鳞癌预后评估中的意义。方法在中文及外文检索工具中系统检索有关TP53蛋白表达与食管鳞癌临床病理特点及预后判断的文献,检索时限为2008年2月-2018年8月。由2名研究员独立筛选文献、提取资料并评估纳入研究的偏倚风险后,采用Review Manager 5.3软件对数据进行荟萃分析。结果共入选24篇病例-对照研究及队列研究的文献,累计病例2 191例。荟萃分析结果显示,中、低分化食管鳞癌TP53基因蛋白阳性表达率明显高于高`分化鳞癌,差异有统计学意义(OR=1.80,P=0.04)。浸润深度中T3+T4的TP53蛋白阳性表达率显著高于T1+T2,差异有统计学意义(OR=2.61,P=0.000 1)。有淋巴结转移病例癌组织中TP53蛋白阳性表达率明显高于无淋巴结转移者,差异有统计学意义(OR=2.27,P=0.000 2)。结论 TP53阳性表达与食管鳞癌临床恶性表型相关,可能是患者不良预后的一个生物标志物,有利于病情评估以及治疗决策的制定。
Objective To estimate the relationship between TP53 expression and prognosis of esophageal squamous cell carcinoma(ESCC). Methods Documents published on foreign language database and Chinese database were searched for study about the relationship between TP53 and clinicopathological characteristics and prognosis of ESCC from February 2008 to August 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then Meta-analysis was performed using RevMan 5.3 software. Results A Total of 2 191 patients from 24 studies were included. The results of meta-analysis showed that the positive expression rate of TP53 in middle and poorly differentiated carcinoma was significantly higher than that in well-differentiated carcinoma, the difference was statistically significant(OR=1.80, P=0.04). The positive expression rate of TP53 in T3+T4 was significantly higher than that in T1+T2; The deeper the degree of infiltration, the higher the positive expression rate of TP53 in cancer tissue, the difference was statistically significant(OR=2.61;P=0.000 1). The positive expression rate of TP53 in cancerous tissues with positive lymph node metastasis was significantly higher than that in patients with negative lymph node metastasis, the difference was statistically significant(OR=2.27, P=0.000 2). Conclusion Meta-analysis showed that the positive expression rate of TP53 was related to the clinical malignant phenotype of ESCC,and TP53 possibly could be used as a biomarker of poor prognosis in patients with esophageal cancer, which is conducive to the treatment of esophageal cancer.
Objective To estimate the relationship between TP53 expression and prognosis of esophageal squamous cell carcinoma(ESCC). Methods Documents published on foreign language database and Chinese database were searched for study about the relationship between TP53 and clinicopathological characteristics and prognosis of ESCC from February 2008 to August 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then Meta-analysis was performed using RevMan 5.3 software. Results A Total of 2 191 patients from 24 studies were included. The results of meta-analysis showed that the positive expression rate of TP53 in middle and poorly differentiated carcinoma was significantly higher than that in well-differentiated carcinoma, the difference was statistically significant(OR=1.80, P=0.04). The positive expression rate of TP53 in T3+T4 was significantly higher than that in T1+T2; The deeper the degree of infiltration, the higher the positive expression rate of TP53 in cancer tissue, the difference was statistically significant(OR=2.61;P=0.000 1). The positive expression rate of TP53 in cancerous tissues with positive lymph node metastasis was significantly higher than that in patients with negative lymph node metastasis, the difference was statistically significant(OR=2.27, P=0.000 2). Conclusion Meta-analysis showed that the positive expression rate of TP53 was related to the clinical malignant phenotype of ESCC,and TP53 possibly could be used as a biomarker of poor prognosis in patients with esophageal cancer, which is conducive to the treatment of esophageal cancer.
引文
[1] 中华人们共和国国家统计局.2008中国统计年签[M].中国统计出版社,2008:450.
[2] TANAKA M,TAKEUCHI H,OSAKI Y,et al.Prognostic significance of circulating tumor cells in patients with advanced esophageal cancer [J].Esophagus,2015,12(4):352-359.
[3] GREENBLATT M S,BENNETT W P,HOLLSTEIN M,et al.Mutation in the p53 tumor suppressor gene:clues to cancer etiology and molecular pathogenesis [J].Cancer Res,1994,54(18):4855-4878.
[4] 王小利,张春梅,施侣元,等.p53基因突变和蛋白表达改变在食管癌预后作用中的Meta分析[J].中华流行病学杂志,2004,25(9):769-774.
[5] 陈安国,于在诚.食管癌癌基因研究进展[J] .实用肿瘤学杂志,2006,20(4):336-339.
[6] CHENG T H ,HSU P K ,LI A F ,et al.Correlation of p53,MDM2 and p14ARF protein expression in human esophageal squamous cell carcinoma[J].J Cancer Res Clin Oncol,2009,135(11):1577-1582.
[7] 犹东,高平.C-myc,P53,bcl-2,CD44V6,rim23-H1基因在食管鳞癌中表达及其与预后的关系[J].宁夏医学杂志,2010,32(3):206-209.
[8] 王伟,李国庆.P53,β-catenin在食管鳞癌的表达及临床意义[J] .潍坊医学院学报,2011,33(1):36-38.
[9] 孙海涛,高宏,张毅,等.p53,PCNA及P-gp在食管癌中表达的研究[J].航空航天医学杂志,2012,23(1):35-37.
[10] 张维彬,梁朝晖,胡少为,等.PTTG,c-myc和 P53在食管癌组织中的表达及其临床意义[J].陕西医学杂志,2009,38(11):1510-1512.
[11] 赵帅,吕文玲.WWOX,p53及Bcl-xl基因在食管鳞癌组织中的表达及其临床意义[J].中国当代医药,2012,19(11):13-15.
[12] 谭家驹,张阳德,杨胜利,等.高发区食管癌组织中 Survivin与 P53蛋白的表达及其临床意义[J].中国现代医学杂志,2008,18(7):936-943.
[13] 李彬.食管癌发生发展过程中p53 蛋白表达的研究[J].河南外科学杂志,2012,18(5):2-4.
[14] 杜日昌,陈玉英,谭丽珊,等.食管癌中Caveolin-1与P53的表达及临床意义[J].中外医学研究,2011,9(14):7-9.
[15] 罗荣,黄克峰,陈德容,等.食管癌中p33ING1 p53蛋白的表达及临床意义[J].中国肿瘤临床,2009,36(6):324-327.
[16] 徐小义,胡坚.食管癌中p53和pRb信号通路变化及临床意义[J].中华实验外科杂志,2016,33(2):505-508.
[17] 毕超,肖创清.食管鳞癌患者P53,VEGF,黏膜端粒酶联合检测及其意义[J].医学临床研究,2013,30(9):1763-1767.
[18] 杨宣琴,李丽,徐恩伟,等.食管鳞状细胞癌中P16和P53蛋白的表达及临床意义[J].中国药物与临床,2009,9(11):1040-1042.
[19] 马丽影,郑湘予,陈奎生.食管鳞状细胞组织中hMLH1,hMSH2及P53蛋白的表达[J].郑州大学学报,2008,43(3):412-414.
[20] 杨宣琴,步鹏,连婧,等.异黏蛋白和 p53 在食管鳞状细胞癌中的表达及意义[J].中国药物与临床,2016,16(8):1103-1105.
[21] 陈丽霞,王娟.P53,Ki-67,LAT1蛋白的异常表达与食管癌癌变过程的关系分析[J].现代消化及介入诊疗,201,22(1):37-39.
[22] 冯怡锟.食管鳞癌组织中P53,Caspase-3蛋白的表达及其临床意义[J].肿瘤基础与临床,2017(5):19-21.
[23] GOCHHAIT S,BHATT A,SHARMA S,et al.Concomitant presence of mutations in mitochondrial genome and p53 in cancerdevelopment-A study in north Indian sporadic breast and esophageal cancer patients[J].Int J Cancer,2008,123(11):2580-2586.
[24] MAKINO T,YAMASAKI M,MIYATA H,et al.p53 mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer[J].Ann Surg Oncol,2010,17(3):804-811.
[25] DEY B ,RAPHAEL V ,KHONGLAH Y ,et al.Immunohistochemical analysis of P53 and PRB in esophageal squamous cell carcinoma[J].J Clin Diagn Res,2014,8(5):1-3.
[26] WANG L H,LI J,HOU J,et al.p53 expression but not p16INK4A correlates with human papillomavirus-associated esophageal squamous cell carcinoma in Kazakh population[J].Infect Agent Cancer,2016,11:19.
[27] RAO X,HUANG D,SUI X,et al.Overexpression of WRAP53 is associated with development and progression of esophageal squamous cell carcinoma[J].Plos One,2014,9(3):e91670.
[28] SANKALECHA T H,GUPTA S J,GAIKWAD N R,et al.Yield of p53 expression in esophageal squamous cell cancer and its relationship with survival[J].Saudi J Gastroenterol,2017,23(5):281-286.
[29] YAO W J,QIN X G,QI B,et al.Association of p53 expression with prognosis in patients with esophageal squamous cell carcinoma[J].Int J Clin Exp Pathol,2014,7(10):7158-7163.
[30] 李翠翠,李苏宜.食管癌突变型 p53过表达临床研究新进展[J].癌症进展,2012,10(3):225-227.
[31] YASUDA M,KUWANO H,WATANABE M,et al.P53 expression in squamous dysplasia associated with carcinoma of the oesophagus:evidence of field carcinogenesis[J].Br J Cancer,2000,83(8):1033-1038.
[32] 王小利,张春梅,施侣元,等.p53基因突变和蛋白表达改变在食管癌预后作用中的Meta分析[J].中华流行病学杂志,2004,25(9):769-774.
[2] TANAKA M,TAKEUCHI H,OSAKI Y,et al.Prognostic significance of circulating tumor cells in patients with advanced esophageal cancer [J].Esophagus,2015,12(4):352-359.
[3] GREENBLATT M S,BENNETT W P,HOLLSTEIN M,et al.Mutation in the p53 tumor suppressor gene:clues to cancer etiology and molecular pathogenesis [J].Cancer Res,1994,54(18):4855-4878.
[4] 王小利,张春梅,施侣元,等.p53基因突变和蛋白表达改变在食管癌预后作用中的Meta分析[J].中华流行病学杂志,2004,25(9):769-774.
[5] 陈安国,于在诚.食管癌癌基因研究进展[J] .实用肿瘤学杂志,2006,20(4):336-339.
[6] CHENG T H ,HSU P K ,LI A F ,et al.Correlation of p53,MDM2 and p14ARF protein expression in human esophageal squamous cell carcinoma[J].J Cancer Res Clin Oncol,2009,135(11):1577-1582.
[7] 犹东,高平.C-myc,P53,bcl-2,CD44V6,rim23-H1基因在食管鳞癌中表达及其与预后的关系[J].宁夏医学杂志,2010,32(3):206-209.
[8] 王伟,李国庆.P53,β-catenin在食管鳞癌的表达及临床意义[J] .潍坊医学院学报,2011,33(1):36-38.
[9] 孙海涛,高宏,张毅,等.p53,PCNA及P-gp在食管癌中表达的研究[J].航空航天医学杂志,2012,23(1):35-37.
[10] 张维彬,梁朝晖,胡少为,等.PTTG,c-myc和 P53在食管癌组织中的表达及其临床意义[J].陕西医学杂志,2009,38(11):1510-1512.
[11] 赵帅,吕文玲.WWOX,p53及Bcl-xl基因在食管鳞癌组织中的表达及其临床意义[J].中国当代医药,2012,19(11):13-15.
[12] 谭家驹,张阳德,杨胜利,等.高发区食管癌组织中 Survivin与 P53蛋白的表达及其临床意义[J].中国现代医学杂志,2008,18(7):936-943.
[13] 李彬.食管癌发生发展过程中p53 蛋白表达的研究[J].河南外科学杂志,2012,18(5):2-4.
[14] 杜日昌,陈玉英,谭丽珊,等.食管癌中Caveolin-1与P53的表达及临床意义[J].中外医学研究,2011,9(14):7-9.
[15] 罗荣,黄克峰,陈德容,等.食管癌中p33ING1 p53蛋白的表达及临床意义[J].中国肿瘤临床,2009,36(6):324-327.
[16] 徐小义,胡坚.食管癌中p53和pRb信号通路变化及临床意义[J].中华实验外科杂志,2016,33(2):505-508.
[17] 毕超,肖创清.食管鳞癌患者P53,VEGF,黏膜端粒酶联合检测及其意义[J].医学临床研究,2013,30(9):1763-1767.
[18] 杨宣琴,李丽,徐恩伟,等.食管鳞状细胞癌中P16和P53蛋白的表达及临床意义[J].中国药物与临床,2009,9(11):1040-1042.
[19] 马丽影,郑湘予,陈奎生.食管鳞状细胞组织中hMLH1,hMSH2及P53蛋白的表达[J].郑州大学学报,2008,43(3):412-414.
[20] 杨宣琴,步鹏,连婧,等.异黏蛋白和 p53 在食管鳞状细胞癌中的表达及意义[J].中国药物与临床,2016,16(8):1103-1105.
[21] 陈丽霞,王娟.P53,Ki-67,LAT1蛋白的异常表达与食管癌癌变过程的关系分析[J].现代消化及介入诊疗,201,22(1):37-39.
[22] 冯怡锟.食管鳞癌组织中P53,Caspase-3蛋白的表达及其临床意义[J].肿瘤基础与临床,2017(5):19-21.
[23] GOCHHAIT S,BHATT A,SHARMA S,et al.Concomitant presence of mutations in mitochondrial genome and p53 in cancerdevelopment-A study in north Indian sporadic breast and esophageal cancer patients[J].Int J Cancer,2008,123(11):2580-2586.
[24] MAKINO T,YAMASAKI M,MIYATA H,et al.p53 mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer[J].Ann Surg Oncol,2010,17(3):804-811.
[25] DEY B ,RAPHAEL V ,KHONGLAH Y ,et al.Immunohistochemical analysis of P53 and PRB in esophageal squamous cell carcinoma[J].J Clin Diagn Res,2014,8(5):1-3.
[26] WANG L H,LI J,HOU J,et al.p53 expression but not p16INK4A correlates with human papillomavirus-associated esophageal squamous cell carcinoma in Kazakh population[J].Infect Agent Cancer,2016,11:19.
[27] RAO X,HUANG D,SUI X,et al.Overexpression of WRAP53 is associated with development and progression of esophageal squamous cell carcinoma[J].Plos One,2014,9(3):e91670.
[28] SANKALECHA T H,GUPTA S J,GAIKWAD N R,et al.Yield of p53 expression in esophageal squamous cell cancer and its relationship with survival[J].Saudi J Gastroenterol,2017,23(5):281-286.
[29] YAO W J,QIN X G,QI B,et al.Association of p53 expression with prognosis in patients with esophageal squamous cell carcinoma[J].Int J Clin Exp Pathol,2014,7(10):7158-7163.
[30] 李翠翠,李苏宜.食管癌突变型 p53过表达临床研究新进展[J].癌症进展,2012,10(3):225-227.
[31] YASUDA M,KUWANO H,WATANABE M,et al.P53 expression in squamous dysplasia associated with carcinoma of the oesophagus:evidence of field carcinogenesis[J].Br J Cancer,2000,83(8):1033-1038.
[32] 王小利,张春梅,施侣元,等.p53基因突变和蛋白表达改变在食管癌预后作用中的Meta分析[J].中华流行病学杂志,2004,25(9):769-774.