组织芯片检测Hh信号通路相关蛋白在前列腺癌中的表达及临床意义
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摘要
探讨Hh(Hedgehog)信号通路相关蛋白Shh、Ptch和Gli在正常前列腺组织和前列腺癌组织中的表达情况和其与临床病例转归特征的相关性。用免疫组化对48例前列腺组织Shh、Ptch和Gli1进行染色,用Image Pro Plus(IPP)图像分析软件定量测试蛋白表达阳性并分析其与临床病理转归特征的关系。发现与正常前列腺组织相比,Shh、Ptch和Gli1在前列腺癌组织中均为高表达,且3种信号因子的表达程度与前列腺癌的临床病理特征具有一定的相关性。说明Hh信号通路在前列腺癌发生发展中起到一定作用。通路成员Shh、Ptch和Glil将成为前列腺癌诊断及判断预后的一项指标。
To investigate the expressions of Shh, Ptch and Gli1 protein of hedgehog signaling pathway in normal prostate tissues and prostate carcinoma tissues, and explore their relationship with clinicopathological features in the prostate cancer. The expression of Shh, Ptch and Gli in prostate carcinoma tissues and normal tissues was examined using immunohistochemical staining. Image Pro Plus(IPP) was used as the method of quantitative image analysis on the relationship between protein expression and clinicopathological features of prostate carcinoma tissues. The expression of Shh, Ptch and Gli1 in Pca was markedly higher compare with normal tissues, the expression of signal factors had a certain correlation with the clinicopathological features. Hedgehog signaling pathway might do a lot in the course of developing and progressing prostate cancer. Shh, Ptch and Gli1 and protein expression might become a prostate cancer diagnosis and prognosis of indicator.
To investigate the expressions of Shh, Ptch and Gli1 protein of hedgehog signaling pathway in normal prostate tissues and prostate carcinoma tissues, and explore their relationship with clinicopathological features in the prostate cancer. The expression of Shh, Ptch and Gli in prostate carcinoma tissues and normal tissues was examined using immunohistochemical staining. Image Pro Plus(IPP) was used as the method of quantitative image analysis on the relationship between protein expression and clinicopathological features of prostate carcinoma tissues. The expression of Shh, Ptch and Gli1 in Pca was markedly higher compare with normal tissues, the expression of signal factors had a certain correlation with the clinicopathological features. Hedgehog signaling pathway might do a lot in the course of developing and progressing prostate cancer. Shh, Ptch and Gli1 and protein expression might become a prostate cancer diagnosis and prognosis of indicator.
引文
Barnett D.H.,Huang H.Y.,Wu X.R.,Laciak R.,Shapiro E.,and Bushman W.,2002,The human prostate expresses sonic hedgehog during fetal development,J.Urol.,168(5):2206-2210
Fan L.,Pepicelli C.V.,Dibble C.C.,Catbagan W.,Zarycki J.L.Laciak R.,Gipp J.,Shaw A.,Lamm M.L.,Munoz A.,Lipinski R.,Thrasher J.B.,and Bushman W.,2004,Hedgehog signaling promotes prostate xenograft tumor growth,Endocrinology,145(8):3961-3970
Han S.J.,Zhang S.W.,Chen W.Q.,and Li C.L.,2013,Analysis of the status and trends of prostate cancer incidence in China Linchuang Zhongliuxue Zazhi(Chinese Clinical Oncology)18(4):330-334(韩苏军,张思维,陈万青,李长岭,2013,中国前列腺癌发病现状和流行趋势分析,临床肿瘤学杂志18(4):330-334)
Katoh Y.,and Katoh M.,2009,Hedgehog target genes:mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation,Curr.Mol.Med.,9(7):873-886
Kim,T.J.,Lee,J.Y.,Hwang T.K.,Kang C.S.,and Choi Y.J.2011,Hedgehog signaling protein expression and its association with prognostic parameters in prostate cancer:a retrospective study from the view point of new 2010 anatomic stage/prognostic groups,J.Surg.Oncol.,104(5):472-479
Li J.,Zhang W.M.,Qiu L.,and Qiu Y.,2013,Analysis of the reliability of tissue microarray in the research of prostate cancer,Shiyong Laonian Yixue(Pract.Geriatr.),27(1):44-46(李江,张炜明,邱梁,邱雁,2013,组织芯片在前列腺癌研究中的可靠性分析,实用老年医学,27(1):44-46)
Liu J.H.,Ding J.D.,Jia W.J.,Li J.M.,Chen J.,Zhang J.S.,Jiang Y.M.,Wang G.,and Zhang H.Y.,2009,The expression and signification of hedgehog signaling pathway effective proteins in prostate cancer and para-cancer tissues,Xiandai Miniao Shengzhi Zhongliu Zazhi(J.Contemp Urol.Reprod Oncol.),1(1):48-50(刘建和,丁建东,贾万健,李炯明,陈戬,张劲松,姜永明,王光,张海燕,2009,Hedgehog信号通路效应蛋白在前列腺癌组织中的表达及意义,现代泌尿生殖肿瘤杂志,1(1):48-50)
Onishi H.,and Katano M.,2011,Hedgehog signaling pathway as a therapeutic target in various types of cancer,Cancer Sci.,102(10):1756-1760
Sanchez P.,Clement V.,and Ruizi I.Altaba A.,2005,Therapeutic targeting of the Hedgehog-GLI pathway in prostate cancer,Cancer Res.,65(8):2990-2992
Sanchez G.M.,Alkhori L.,Hatano E.,Schultz S.W.,Kuzhandaivel A.,Jafari S.,Granseth B.,and Alenius M.,2016,Hedgehog signaling regulates the ciliary transport of odorant receptors in drosophila,Cell Rep.,14(3):464-470
Sanchez P.,Hernández A.M.,Stecca B.,Kahler A.J.,De Gueme A.M.,Barrett A.,Beyna M.,Datta M.W.,Datta S.,and Ruizi Altaba A.,2004,Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling,Proc.Natl.Acad.Sci.USA,101(34):12561-12566
Scales S.J.,and de Sauvage F.J.,2009,Mechanisms of Hedgehog pathway activation in cancer and implications for therapy,Trends Pharmacol.Sci.,30(6):303-312
Shaw A.,and Bushman W.,2007,Hedgehog signaling in the prostate,J.Urol.,177(3):832-838
Stecca B.,Mas C.,and Ruiz i Altaba A.,2005,Interference with HH-GLI signaling inhibits prostate cancer,Trends Mol.Med.,11(5):199-203
Torre L.A.,Bray F.,Siegel R.L.,Ferlay J.,Lortet-Tieulent J.,and Jemal A.,2015,Global cancer statistics,2012,CA Cancer J.Clin.,65(2):87-108
Tzelepi V.,Karlou M.,Wen S.,Hoang A.,Logothetis C.,Troncoso P.,and Efstathiou E.,2011,Expression of hedgehog pathway components in prostate carcinoma microenvironment:shifting the balance towards autocrine signalling,Histopathology,58(7):1037-1047
Zhai J.P.,Wang J.W.,Li G.Z.,Wang H.,Wang H.D.,He F.,Huang G.L.,and Man L.B.,2015,Prognostic factors in hormone sensitive metastatic prostate cancer,Zhongguo Xiandai Yixue Zazhi(China Journal of Modern Medicine),25(3):31-35(翟建坡,王建伟,李贵忠,王海,王海东,何峰,黄广林,满立波,2015,激素敏感转移性前列腺癌预后因素分析,中国现代医学杂志,25(3):31-35)
Fan L.,Pepicelli C.V.,Dibble C.C.,Catbagan W.,Zarycki J.L.Laciak R.,Gipp J.,Shaw A.,Lamm M.L.,Munoz A.,Lipinski R.,Thrasher J.B.,and Bushman W.,2004,Hedgehog signaling promotes prostate xenograft tumor growth,Endocrinology,145(8):3961-3970
Han S.J.,Zhang S.W.,Chen W.Q.,and Li C.L.,2013,Analysis of the status and trends of prostate cancer incidence in China Linchuang Zhongliuxue Zazhi(Chinese Clinical Oncology)18(4):330-334(韩苏军,张思维,陈万青,李长岭,2013,中国前列腺癌发病现状和流行趋势分析,临床肿瘤学杂志18(4):330-334)
Katoh Y.,and Katoh M.,2009,Hedgehog target genes:mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation,Curr.Mol.Med.,9(7):873-886
Kim,T.J.,Lee,J.Y.,Hwang T.K.,Kang C.S.,and Choi Y.J.2011,Hedgehog signaling protein expression and its association with prognostic parameters in prostate cancer:a retrospective study from the view point of new 2010 anatomic stage/prognostic groups,J.Surg.Oncol.,104(5):472-479
Li J.,Zhang W.M.,Qiu L.,and Qiu Y.,2013,Analysis of the reliability of tissue microarray in the research of prostate cancer,Shiyong Laonian Yixue(Pract.Geriatr.),27(1):44-46(李江,张炜明,邱梁,邱雁,2013,组织芯片在前列腺癌研究中的可靠性分析,实用老年医学,27(1):44-46)
Liu J.H.,Ding J.D.,Jia W.J.,Li J.M.,Chen J.,Zhang J.S.,Jiang Y.M.,Wang G.,and Zhang H.Y.,2009,The expression and signification of hedgehog signaling pathway effective proteins in prostate cancer and para-cancer tissues,Xiandai Miniao Shengzhi Zhongliu Zazhi(J.Contemp Urol.Reprod Oncol.),1(1):48-50(刘建和,丁建东,贾万健,李炯明,陈戬,张劲松,姜永明,王光,张海燕,2009,Hedgehog信号通路效应蛋白在前列腺癌组织中的表达及意义,现代泌尿生殖肿瘤杂志,1(1):48-50)
Onishi H.,and Katano M.,2011,Hedgehog signaling pathway as a therapeutic target in various types of cancer,Cancer Sci.,102(10):1756-1760
Sanchez P.,Clement V.,and Ruizi I.Altaba A.,2005,Therapeutic targeting of the Hedgehog-GLI pathway in prostate cancer,Cancer Res.,65(8):2990-2992
Sanchez G.M.,Alkhori L.,Hatano E.,Schultz S.W.,Kuzhandaivel A.,Jafari S.,Granseth B.,and Alenius M.,2016,Hedgehog signaling regulates the ciliary transport of odorant receptors in drosophila,Cell Rep.,14(3):464-470
Sanchez P.,Hernández A.M.,Stecca B.,Kahler A.J.,De Gueme A.M.,Barrett A.,Beyna M.,Datta M.W.,Datta S.,and Ruizi Altaba A.,2004,Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling,Proc.Natl.Acad.Sci.USA,101(34):12561-12566
Scales S.J.,and de Sauvage F.J.,2009,Mechanisms of Hedgehog pathway activation in cancer and implications for therapy,Trends Pharmacol.Sci.,30(6):303-312
Shaw A.,and Bushman W.,2007,Hedgehog signaling in the prostate,J.Urol.,177(3):832-838
Stecca B.,Mas C.,and Ruiz i Altaba A.,2005,Interference with HH-GLI signaling inhibits prostate cancer,Trends Mol.Med.,11(5):199-203
Torre L.A.,Bray F.,Siegel R.L.,Ferlay J.,Lortet-Tieulent J.,and Jemal A.,2015,Global cancer statistics,2012,CA Cancer J.Clin.,65(2):87-108
Tzelepi V.,Karlou M.,Wen S.,Hoang A.,Logothetis C.,Troncoso P.,and Efstathiou E.,2011,Expression of hedgehog pathway components in prostate carcinoma microenvironment:shifting the balance towards autocrine signalling,Histopathology,58(7):1037-1047
Zhai J.P.,Wang J.W.,Li G.Z.,Wang H.,Wang H.D.,He F.,Huang G.L.,and Man L.B.,2015,Prognostic factors in hormone sensitive metastatic prostate cancer,Zhongguo Xiandai Yixue Zazhi(China Journal of Modern Medicine),25(3):31-35(翟建坡,王建伟,李贵忠,王海,王海东,何峰,黄广林,满立波,2015,激素敏感转移性前列腺癌预后因素分析,中国现代医学杂志,25(3):31-35)