MTA1表达与中国肺癌患者预后关系的meta分析
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摘要
背景与目的已有的研究表明:在多种恶性肿瘤中发现转移相关蛋白1(metastasis associated protein1,MTA1)发挥着促进肿瘤侵袭与转移的作用,且与肿瘤患者预后不佳有关。目前MTA1在肺癌中的预后作用仍有争议,故我们采用meta分析的方法评估其在肺癌患者中的预后价值。方法通过计算机检索PubMed、Embase、万方数据库、中国生物医学文献数据库、中国知网等数据库,收集纳入研究MTA1表达与肺癌预后关系的文献及相关数据,采用Stata 12.0软件进行数据分析,合并值为风险比(hazard ratio,HR)。结果总共纳入8项研究共712例中国肺癌患者,对这些研究进行异质性检验,发现存在异质性(I~2=59.0%,P=0.017),故采用随机效应模型进行数据合并得HR=2.07(95%CI:1.42-3.02,P<0.001)。同时分层分析显示在非小细胞肺癌(non-small cell lung cancer,NSCLC)中各研究无明显异质性(I~2=47.0%,P=0.093),采用固定效应模型合并得HR=1.66(95%CI:1.27-2.18,P<0.001)。结论 MTA1高表达可能是中国NSCLC患者预后不良的一个指标,在肺癌及小细胞肺癌中的预后价值尚缺乏证据。
Background and objective It has been proven that metastasis associated protein 1(MTA1) was correlated with tumor invasion and migration and poor prognosis of several malignant carcinomas. The prognostic role of MTA1 expression in lung cancer remained controversial, we performed this meta-analysis to assess the prognostic value of MTA1 expression in lung cancer. Methods A systematic literature search was conducted to identify eligible studies which dealing with the relationship between MTA1 expression and prognosis of lung cancer in PubMed, Embase, Wanfang databases, China Biology Medicine disc and China National Knowledge Infrastructure. The pooled hazard ratio(HR) were used to assess the relationship between MTA1 expression and prognosis of lung cancer. All data were analysed using the Stata 12.0 software. Results A total of 712 Chinese lung cancer patients from 8 studies were included in this meta-analysis. There was significant heterogeneity existed in these studies(I~2=59.0%, P=0.017), so we used a random effects model to calculate the pooled HR=2.07(95%CI: 1.42-3.02, P<0.001). At the same time, we observed through stratified analysis by histology that there was no significant heterogeneity in non-small cell lung cancer(NSCLC), and the fixed effects model was used to calculate the pooled HR=1.66(95%CI: 1.27-2.18, P<0.001). Conclusion Overexpression of MTA1 could be a marker of poor prognosis in Chinese NSCLC patients, but not in lung cancer or small cell lung cancer. Additional studies with larger samples and well-designed were required to derive the more precise outcome.
Background and objective It has been proven that metastasis associated protein 1(MTA1) was correlated with tumor invasion and migration and poor prognosis of several malignant carcinomas. The prognostic role of MTA1 expression in lung cancer remained controversial, we performed this meta-analysis to assess the prognostic value of MTA1 expression in lung cancer. Methods A systematic literature search was conducted to identify eligible studies which dealing with the relationship between MTA1 expression and prognosis of lung cancer in PubMed, Embase, Wanfang databases, China Biology Medicine disc and China National Knowledge Infrastructure. The pooled hazard ratio(HR) were used to assess the relationship between MTA1 expression and prognosis of lung cancer. All data were analysed using the Stata 12.0 software. Results A total of 712 Chinese lung cancer patients from 8 studies were included in this meta-analysis. There was significant heterogeneity existed in these studies(I~2=59.0%, P=0.017), so we used a random effects model to calculate the pooled HR=2.07(95%CI: 1.42-3.02, P<0.001). At the same time, we observed through stratified analysis by histology that there was no significant heterogeneity in non-small cell lung cancer(NSCLC), and the fixed effects model was used to calculate the pooled HR=1.66(95%CI: 1.27-2.18, P<0.001). Conclusion Overexpression of MTA1 could be a marker of poor prognosis in Chinese NSCLC patients, but not in lung cancer or small cell lung cancer. Additional studies with larger samples and well-designed were required to derive the more precise outcome.
引文
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2 Siegel RL,Miller KD,Jemal A.Cancer statistics,2015.CA Cancer J Clin,2015,65(1):5-29.
3 Kaur E,Gupta S,Dutt S.Clinical implications of MTA proteins in human cancer.Cancer Metastasis Rev,2014,33(4):1017-1024.
4 Toh Y,Nicolson GL.Properties and clinical relevance of MTA1protein in human cancer.Cancer Metastasis Rev,2014,33(4):891-900.
5 Jang KS,Paik SS,Chung H,et al.MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers.Cancer Sci,2006,97(5):374-379.
6 Higashijima J,Kurita N,Miyatani T,et al.Expression of histone deacetylase 1 and metastasis-associated protein 1 as prognostic factors in colon cancer.Oncol Rep,2011,26(2):343-348.
7 Song L,Wang Z,Li u X.MTA1:a prognosi s indicator of postoperat ive patients with esophageal carcinoma.Thorac Cardiovasc Surg,2013,61(6):479-485.
8 Deng X,Du L,Wang C,et al.Close association of metastasisassociated protein 1 overexpression with increased angiogenesis and poor survival in patients with histologically node-negative gastric cancer.World J Surg,2013,37(4):792-798.
9 Ning Z,Gan J,Chen C,et al.Molecular functions and significance of the MTA family in hormone-independent cancer.Cancer Metastasis Rev,2014,33(4):901-919.
10 Ma K,Fan Y,Dong X,e t al.MTA1 promotes epi thel ial to mesenchymal transition and metastasis in non-small-cell lung cancer.Oncotarget,2017,8(24):38825-38840.
11 Zhou N,Wang H,Liu H,et al.MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer.J Exp Clin Cancer Res,2015,34:157.
12 Zhang N,Zhang QF,Wang EH,et al.Relationship between metastasis-associated protein 1 expression and metastasis and prognosis in non-small cell lung cancer.Zhongguo Fei Ai Za Zhi,2007,10(4):279-283.[张楠,张清富,王恩华,等.转移相关蛋白1与非小细胞肺癌转移及预后关系研究.中国肺癌杂志,2007,10(4):279-283.]
13 Wang J,Sheng Z,Yang W,et al.Elevated serum concentration of chitinase 3-like 1 is an independent prognostic biomarker for poor survival in lung cancer patients.Cell Physiol Biochem,2016,38(2):461-468.
14 Begg CB,Mazumdar M.Operating character istics of a rank correlation test for publication bias.Biometrics,1994,50(4):1088-1101.
15 Egger M,Davey SG,Schneider M,et al.Bias in meta-analysis detected by a simple,graphical test.BMJ,1997,315(7109):629-634.
16 Zhu X,Guo Y,Li X,et al.Metastasis-associated protein 1 nuclear expression is associated with tumor progression and clinical outcome in patients with non-small cell lung cancer.J Thorac Oncol,2010,5(8):1159-1166.
17 Li SH,Tian H,Yue WM,et al.Overexpression of metastasisassociated protein 1 issignificantly correlated with tumor angiogenesis and poor survival in patients with early-stage nonsmall cell lung cancer.Ann Surg Oncol,2011,18(7):2048-2056.
18 Yu Y,Wang Z,Zhang MY,et al.Relation between prognosis and expression of metastasis-associated protein 1 in stage I non-small cell lung cancer.Interact Cardiovasc Thorac Surg,2011,12(2):166-169.
19 Chen YT,Xu YC,Tao LL,et al.Expression of MTA1 protein in small cell lung cancer and its correlation with chemotherapy sensitivity and prognosis.Lin Chuang Zhong Liu Xue Za Zhi,2014(2):102-106.[陈一天,徐益琛,陶累累,等.小细胞肺癌中MTA1蛋白的表达及其与化疗敏感性和预后的关系.临床肿瘤学杂志,2014(2):102-106.]
20 Li S,Tian H,Yue W,et al.Clinicopathological and prognostic significance of metastasis-associated protein 1 expression and its correlation with angiogenesis in lung invasive adenocarcinomas,based on the 2011 IASLC/ATS/ERS classification.Oncol Lett,2016,11(1):224-230.
21 Parmar MK,Torri V,Stewart L.Extracting summar y statistics to perform meta-analyses of the published literature for survival endpoints.Stat Med,1998,17(24):2815-2834.
22 Kisluk J,Ciborowski M,Niemira M,et al.Proteomics biomarkers for non-small cell lung cancer.J Pharm Biomed Anal,2014,101:40-49.
23 Li DQ,Pakala SB,Nair SS,et al.Metastasis-associated protein1/nucleosome remodeling and histone deacetylase complex in cancer.Cancer Res,2012,72(2):387-394.
24 Luo H,Li H,Yao N,et al.Metastasis-associated protein 1 as a new prognostic marker for solid tumors:a meta-analysis of cohort studies.Tumour Biol,2014,35(6):5823-5832.
25 Moon HE,Cheon H,Lee MS.Metastasis-associated protein1 inhibits p53-induced apoptosis.Oncol Rep,2007,18(5):1311-1314.
26 Yoo YG,Kong G,Lee MO.Metastasi s-associated protein 1enhances stability of hypoxia-inducible factor-1alpha protein by recr uiting histone deacetylase 1.EMBO J,2006,25(6):1231-1241.
27 Pakala SB,Singh K,Reddy SD,et al.TGF-β1 signaling targets metastasis-associated protein 1,a new effector in epithelial cells.Oncogene,2011,30(19):2230-2241.
28 Dannenmann C,Shabani N,Fr iese K,et al.The metastasisassociated gene MTA1 is upregulated in advanced ovarian cancer,represses ERbeta,and enhances expression of oncogenic cytokine GRO.Cancer Biol Ther,2008,7(9):1460-1467.
2 Siegel RL,Miller KD,Jemal A.Cancer statistics,2015.CA Cancer J Clin,2015,65(1):5-29.
3 Kaur E,Gupta S,Dutt S.Clinical implications of MTA proteins in human cancer.Cancer Metastasis Rev,2014,33(4):1017-1024.
4 Toh Y,Nicolson GL.Properties and clinical relevance of MTA1protein in human cancer.Cancer Metastasis Rev,2014,33(4):891-900.
5 Jang KS,Paik SS,Chung H,et al.MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers.Cancer Sci,2006,97(5):374-379.
6 Higashijima J,Kurita N,Miyatani T,et al.Expression of histone deacetylase 1 and metastasis-associated protein 1 as prognostic factors in colon cancer.Oncol Rep,2011,26(2):343-348.
7 Song L,Wang Z,Li u X.MTA1:a prognosi s indicator of postoperat ive patients with esophageal carcinoma.Thorac Cardiovasc Surg,2013,61(6):479-485.
8 Deng X,Du L,Wang C,et al.Close association of metastasisassociated protein 1 overexpression with increased angiogenesis and poor survival in patients with histologically node-negative gastric cancer.World J Surg,2013,37(4):792-798.
9 Ning Z,Gan J,Chen C,et al.Molecular functions and significance of the MTA family in hormone-independent cancer.Cancer Metastasis Rev,2014,33(4):901-919.
10 Ma K,Fan Y,Dong X,e t al.MTA1 promotes epi thel ial to mesenchymal transition and metastasis in non-small-cell lung cancer.Oncotarget,2017,8(24):38825-38840.
11 Zhou N,Wang H,Liu H,et al.MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer.J Exp Clin Cancer Res,2015,34:157.
12 Zhang N,Zhang QF,Wang EH,et al.Relationship between metastasis-associated protein 1 expression and metastasis and prognosis in non-small cell lung cancer.Zhongguo Fei Ai Za Zhi,2007,10(4):279-283.[张楠,张清富,王恩华,等.转移相关蛋白1与非小细胞肺癌转移及预后关系研究.中国肺癌杂志,2007,10(4):279-283.]
13 Wang J,Sheng Z,Yang W,et al.Elevated serum concentration of chitinase 3-like 1 is an independent prognostic biomarker for poor survival in lung cancer patients.Cell Physiol Biochem,2016,38(2):461-468.
14 Begg CB,Mazumdar M.Operating character istics of a rank correlation test for publication bias.Biometrics,1994,50(4):1088-1101.
15 Egger M,Davey SG,Schneider M,et al.Bias in meta-analysis detected by a simple,graphical test.BMJ,1997,315(7109):629-634.
16 Zhu X,Guo Y,Li X,et al.Metastasis-associated protein 1 nuclear expression is associated with tumor progression and clinical outcome in patients with non-small cell lung cancer.J Thorac Oncol,2010,5(8):1159-1166.
17 Li SH,Tian H,Yue WM,et al.Overexpression of metastasisassociated protein 1 issignificantly correlated with tumor angiogenesis and poor survival in patients with early-stage nonsmall cell lung cancer.Ann Surg Oncol,2011,18(7):2048-2056.
18 Yu Y,Wang Z,Zhang MY,et al.Relation between prognosis and expression of metastasis-associated protein 1 in stage I non-small cell lung cancer.Interact Cardiovasc Thorac Surg,2011,12(2):166-169.
19 Chen YT,Xu YC,Tao LL,et al.Expression of MTA1 protein in small cell lung cancer and its correlation with chemotherapy sensitivity and prognosis.Lin Chuang Zhong Liu Xue Za Zhi,2014(2):102-106.[陈一天,徐益琛,陶累累,等.小细胞肺癌中MTA1蛋白的表达及其与化疗敏感性和预后的关系.临床肿瘤学杂志,2014(2):102-106.]
20 Li S,Tian H,Yue W,et al.Clinicopathological and prognostic significance of metastasis-associated protein 1 expression and its correlation with angiogenesis in lung invasive adenocarcinomas,based on the 2011 IASLC/ATS/ERS classification.Oncol Lett,2016,11(1):224-230.
21 Parmar MK,Torri V,Stewart L.Extracting summar y statistics to perform meta-analyses of the published literature for survival endpoints.Stat Med,1998,17(24):2815-2834.
22 Kisluk J,Ciborowski M,Niemira M,et al.Proteomics biomarkers for non-small cell lung cancer.J Pharm Biomed Anal,2014,101:40-49.
23 Li DQ,Pakala SB,Nair SS,et al.Metastasis-associated protein1/nucleosome remodeling and histone deacetylase complex in cancer.Cancer Res,2012,72(2):387-394.
24 Luo H,Li H,Yao N,et al.Metastasis-associated protein 1 as a new prognostic marker for solid tumors:a meta-analysis of cohort studies.Tumour Biol,2014,35(6):5823-5832.
25 Moon HE,Cheon H,Lee MS.Metastasis-associated protein1 inhibits p53-induced apoptosis.Oncol Rep,2007,18(5):1311-1314.
26 Yoo YG,Kong G,Lee MO.Metastasi s-associated protein 1enhances stability of hypoxia-inducible factor-1alpha protein by recr uiting histone deacetylase 1.EMBO J,2006,25(6):1231-1241.
27 Pakala SB,Singh K,Reddy SD,et al.TGF-β1 signaling targets metastasis-associated protein 1,a new effector in epithelial cells.Oncogene,2011,30(19):2230-2241.
28 Dannenmann C,Shabani N,Fr iese K,et al.The metastasisassociated gene MTA1 is upregulated in advanced ovarian cancer,represses ERbeta,and enhances expression of oncogenic cytokine GRO.Cancer Biol Ther,2008,7(9):1460-1467.