乳腺癌组织中凋亡抑制蛋白Apollon的表达及其临床意义
|
摘要
目的研究乳腺癌组织中凋亡抑制蛋白Apollon免疫组化表达及临床意义。方法回顾性收集解放军第四二二医院2010年1月至2014年12月手术切除的女性乳腺癌组织标本66例,采用免疫组织化学法检测66例乳腺癌组织中Apollon、HER-2及survivin的表达。采用Kendall等级相关检验分析Apollon表达与HER-2表达、survivin表达、肿瘤大小及淋巴结状态之间的相关性。结果在乳腺癌组织中Apollon、HER-2及survivin的阳性表达率分别为59.1%(39/66)、31.8%(21/66)及39.4%(26/66)。Apollon表达与HER-2表达(tau-b=0.370,P=0.003)、survivin表达(tau-b=0.292,P=0.018)、肿瘤大小(tau-b=0.322,P=0.009)及淋巴结状态(tau-b=0.424,P=0.001)显著相关。结论 Apollon表达与HER-2表达、Survivin表达、肿瘤大小及淋巴结状态有关,其可能是一个与乳腺癌发展相关的潜在分子标志物。
Objective To investigate the immunohistochemical expression of apoptosis protein inhibitor Apollon in breast cancer tissue and its clinical significance. Methods We retrospectively analyzed the female breast cancer tissue specimens from 66 cases treated in No. 422 Hospital of PLA from January 2010 and December 2014. The expressions of Apollon,HER-2 and survivin were assessed immunohistochemically. The correlation of Apollon expression with HER-2 expression,survivin expression,tumor size and lymph node status was analyzed using Kendall rank correlation test. Results The positive rates of Apollon,HER-2 and survivin in breast cancer tissue were 59. 1%( 39 /66),31. 8%( 21 /66) and 39. 4%( 26 /66),respectively. Apollon expression was significantly associated with HER-2 expression( tau-b = 0. 370,P = 0. 003),survivin expression( tau-b = 0. 292,P =0. 018),tumor size( tau-b =0. 322,P =0. 009) and lymph node status( tau-b =0. 424,P= 0. 001). Conclusions Apollon expression is associated with HER-2 expression,survivin expression,tumor size and lymph node status. Apollon may be a potential molecular marker in the development of breast cancer.
Objective To investigate the immunohistochemical expression of apoptosis protein inhibitor Apollon in breast cancer tissue and its clinical significance. Methods We retrospectively analyzed the female breast cancer tissue specimens from 66 cases treated in No. 422 Hospital of PLA from January 2010 and December 2014. The expressions of Apollon,HER-2 and survivin were assessed immunohistochemically. The correlation of Apollon expression with HER-2 expression,survivin expression,tumor size and lymph node status was analyzed using Kendall rank correlation test. Results The positive rates of Apollon,HER-2 and survivin in breast cancer tissue were 59. 1%( 39 /66),31. 8%( 21 /66) and 39. 4%( 26 /66),respectively. Apollon expression was significantly associated with HER-2 expression( tau-b = 0. 370,P = 0. 003),survivin expression( tau-b = 0. 292,P =0. 018),tumor size( tau-b =0. 322,P =0. 009) and lymph node status( tau-b =0. 424,P= 0. 001). Conclusions Apollon expression is associated with HER-2 expression,survivin expression,tumor size and lymph node status. Apollon may be a potential molecular marker in the development of breast cancer.
引文
[1]Chen W,Zheng R,Zeng H,et al.Annual report on status of cancer in China,2011[J].Chin J Cancer Res,2015;27(1):2-12.
[2]Pennati M,Millo E,Gandellini P,et al.RNA interferencemediated validation of survivin and Apollon/BRUCE as new therapeutic targets for cancer therapy[J].Curr Top Med Chem,2012,12(2):69-78.
[3]宫惠琳,张锁平,张冠军,等.Survivin、MMP-2在乳腺癌中的表达及其相关性研究[J].重庆医科大学学报,2012,37(2):106-109.
[4]曹丹霞,何建蓉,沈坤炜,等.激素受体和HER-2及Ki-67预测乳腺癌新辅助化疗疗效价值的分析[J].中华肿瘤防治杂志,2012,19(13):1000-1003.
[5]Cotter TG.Apoptosis and cancer:the genesis of a research field[J].Nat Rev Cancer,2009,9(7):501-507.
[6]Deveraux QL,Reed JC.IAP family proteins--suppressors of apoptosis[J].Genes Dev,1999,13(3):239-252.
[7]Hauser HP,Bardroff M,Pyrowolakis G,et al.A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors[J].J Cell Biol,1998,141(6):1415-1422.
[8]Qiu XB,Goldberg AL.The membrane-associated inhibitor of apoptosis protein,BRUCE/Apollon,antagonizes both the precursor and mature forms of Smac and caspase-9[J].J Biol Chem,2005,280(1):174-182.
[9]Hao Y,Sekine K,Kawabata A,et al.Apollon ubiquitinates SMAC and caspase-9,and has an essential cytoprotection function[J].Nat Cell Biol,2004,6(9):849-860.
[10]Ismail EA,Mahmoud HM,Tawfik LM,et al.BIRC6/Apollon gene expression in childhood acute leukemia:impact on therapeutic response and prognosis[J].Eur J Haematol,2012,88(2):118-127.
[11]Low CG,Luk IS,Lin D,et al.BIRC6 protein,an inhibitor of apoptosis:role in survival of human prostate cancer cells[J].PLo S One,2013,8(2):e55837.
[12]Wang L,Chen YJ,Hou J,et al.Expression and clinical significance of BIRC6 in human epithelial ovarian cancer[J].Tumour Biol,2014,35(5):4891-4896.
[13]罗力亚,刘风玲.HER2/neu在肿瘤中研究进展及抗HER2/neu治疗[J].现代肿瘤医学,2011,19(12):2573-2576.
[14]Barnes DM.c-erb B-2 amplification in mammary carcinoma[J].J Cell Biochem Suppl,1993,17G:132-138.
[15]董营,康丽花,关萌,等.乳腺癌患者术后辅助治疗的临床效果及其影响因素分析[J].吉林大学学报(医学版),2015,41(3):636-642.
[16]Song J,Su H,Zhou YY,et al.Prognostic value of survivin expression in breast cancer patients:a meta-analysis[J].Tumour Biol,2013,34(4):2053-2062.
[17]陈建发,岳志强,傅明,等.新辅助化疗前apollon在乳腺癌组织中的表达及意义[J].南方医科大学学报,2015,35(8):1201-1205.
[18]李庆霞,颜聪亚,闫晓路,等.乳腺浸润性导管癌组织FGFR1和Survivin表达临床意义分析[J].中华肿瘤防治杂志,2013,20(17):1315-1318.
[19]Zhang H,Jin F.HER-2 expression correlates with survivin in primary invasive ductal breast cancers[J].Asian Pac J Cancer Prev,2010,11(5):1201-1204.
[20]Ryan BM,Konecny GE,Kahlert S,et al.Survivin expression in breast cancer predicts clinical outcome and is associated with HER2,VEGF,urokinase plasminogen activator and PAI-1[J].Ann Oncol,2006,17(4):597-604.
[21]Fuzhong T,Nan L,Jiajia G,et al.Clinical significance of the relationship between expression of survivin and effects of neoadjuvant chemotherapy in locally advanced breast cancer[J].Gan To Kagaku Ryoho,2008,35(8):1319-1323.
[22]Zhang M,Zhang X,Zhao S,et al.Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer(TNBC)patients[J].Target Oncol,2014,9(4):349-357.
[23]张真,张小涛,于兰,等.乳腺癌CD44v6和Survivin的表达与临床预后的相关性研究[J].中国肿瘤临床,2011,38(14):835-838.
[24]桑占发,王兴,齐玉新,等.survivin在乳腺癌中的表达及其与Ki-67和c-erb B-2表达的关系[J].肿瘤防治研究,2010,37(7):773-776.
[2]Pennati M,Millo E,Gandellini P,et al.RNA interferencemediated validation of survivin and Apollon/BRUCE as new therapeutic targets for cancer therapy[J].Curr Top Med Chem,2012,12(2):69-78.
[3]宫惠琳,张锁平,张冠军,等.Survivin、MMP-2在乳腺癌中的表达及其相关性研究[J].重庆医科大学学报,2012,37(2):106-109.
[4]曹丹霞,何建蓉,沈坤炜,等.激素受体和HER-2及Ki-67预测乳腺癌新辅助化疗疗效价值的分析[J].中华肿瘤防治杂志,2012,19(13):1000-1003.
[5]Cotter TG.Apoptosis and cancer:the genesis of a research field[J].Nat Rev Cancer,2009,9(7):501-507.
[6]Deveraux QL,Reed JC.IAP family proteins--suppressors of apoptosis[J].Genes Dev,1999,13(3):239-252.
[7]Hauser HP,Bardroff M,Pyrowolakis G,et al.A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors[J].J Cell Biol,1998,141(6):1415-1422.
[8]Qiu XB,Goldberg AL.The membrane-associated inhibitor of apoptosis protein,BRUCE/Apollon,antagonizes both the precursor and mature forms of Smac and caspase-9[J].J Biol Chem,2005,280(1):174-182.
[9]Hao Y,Sekine K,Kawabata A,et al.Apollon ubiquitinates SMAC and caspase-9,and has an essential cytoprotection function[J].Nat Cell Biol,2004,6(9):849-860.
[10]Ismail EA,Mahmoud HM,Tawfik LM,et al.BIRC6/Apollon gene expression in childhood acute leukemia:impact on therapeutic response and prognosis[J].Eur J Haematol,2012,88(2):118-127.
[11]Low CG,Luk IS,Lin D,et al.BIRC6 protein,an inhibitor of apoptosis:role in survival of human prostate cancer cells[J].PLo S One,2013,8(2):e55837.
[12]Wang L,Chen YJ,Hou J,et al.Expression and clinical significance of BIRC6 in human epithelial ovarian cancer[J].Tumour Biol,2014,35(5):4891-4896.
[13]罗力亚,刘风玲.HER2/neu在肿瘤中研究进展及抗HER2/neu治疗[J].现代肿瘤医学,2011,19(12):2573-2576.
[14]Barnes DM.c-erb B-2 amplification in mammary carcinoma[J].J Cell Biochem Suppl,1993,17G:132-138.
[15]董营,康丽花,关萌,等.乳腺癌患者术后辅助治疗的临床效果及其影响因素分析[J].吉林大学学报(医学版),2015,41(3):636-642.
[16]Song J,Su H,Zhou YY,et al.Prognostic value of survivin expression in breast cancer patients:a meta-analysis[J].Tumour Biol,2013,34(4):2053-2062.
[17]陈建发,岳志强,傅明,等.新辅助化疗前apollon在乳腺癌组织中的表达及意义[J].南方医科大学学报,2015,35(8):1201-1205.
[18]李庆霞,颜聪亚,闫晓路,等.乳腺浸润性导管癌组织FGFR1和Survivin表达临床意义分析[J].中华肿瘤防治杂志,2013,20(17):1315-1318.
[19]Zhang H,Jin F.HER-2 expression correlates with survivin in primary invasive ductal breast cancers[J].Asian Pac J Cancer Prev,2010,11(5):1201-1204.
[20]Ryan BM,Konecny GE,Kahlert S,et al.Survivin expression in breast cancer predicts clinical outcome and is associated with HER2,VEGF,urokinase plasminogen activator and PAI-1[J].Ann Oncol,2006,17(4):597-604.
[21]Fuzhong T,Nan L,Jiajia G,et al.Clinical significance of the relationship between expression of survivin and effects of neoadjuvant chemotherapy in locally advanced breast cancer[J].Gan To Kagaku Ryoho,2008,35(8):1319-1323.
[22]Zhang M,Zhang X,Zhao S,et al.Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer(TNBC)patients[J].Target Oncol,2014,9(4):349-357.
[23]张真,张小涛,于兰,等.乳腺癌CD44v6和Survivin的表达与临床预后的相关性研究[J].中国肿瘤临床,2011,38(14):835-838.
[24]桑占发,王兴,齐玉新,等.survivin在乳腺癌中的表达及其与Ki-67和c-erb B-2表达的关系[J].肿瘤防治研究,2010,37(7):773-776.