Livin、Caspase-3和Bcl-2在非小細胞肺癌;的表達及生存分析_《中國呼吸與危重監護雜志》

作者：

鄭春晨 ¹ ,  陳愉生 ¹ , 陳小巖 ² , 李鴻茹 ³

1 福建醫科大學省立臨床學院呼吸內科（福建福州 350004）;;
2 福建省立醫院病理科（福建福州 350001）;;
3 福建省立醫院呼吸內科（福建福州 350001）;

關鍵詞：

非小細胞肺癌 Livin 半胱氨酸天冬氨酸蛋白酶3 Bcl-2 預后

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目的探討Livin 在非小細胞肺癌( NSCLC) 中的表達, 及與NSCLC 病理、生物學行為指標和預后的關系。方法采用免疫組織化學法檢測87 例NSCLC 腫瘤組織和40 例肺良性組織中 Livin、Caspase-3 和Bcl-2 蛋白的表達情況, 將其表達與NSCLC 病理、生物學行為等指標進行相關分析。多因素COX 回歸生存分析探討Livin、Caspase-3 和Bcl-2 蛋白表達水平與預后的關系。結果 Livin 和Bcl-2 蛋白在肺癌組織中的表達明顯高于在肺良性病變組織中的表達( 72. 41% 比0. 0% ,74. 71% 比0. 0%, P = 0. 000) , Caspase-3 蛋白表達則明顯降低( 67. 82% 比87. 5% , P lt; 0. 05) 。Livin、Caspase-3 和Bcl-2 表達主要位于胞漿, 未見核內表達。其表達與肺癌的組織細胞類型、分化程度、淋巴結轉移、TNM分期、腫瘤大小以及部位無明顯相關性。在NSCLC 中, Livin 蛋白表達與Caspase-3 和Bcl-2 蛋白表達有相關性( r1 = - 0. 260, P = 0. 015; r2 =0. 351, P =0. 001) 。Livin、Caspase-3 和Bcl-2 不是影響肺癌手術患者預后的獨立預后因素。結論 Livin 蛋白、Bcl-2 蛋白在肺癌組織中表達上調,Livin 的表達與Caspase-3、Bcl-2 蛋白的表達呈相關性, 三者在肺癌的發生發展中可能起協同作用。Livin、Bcl-2 和Caspase-3 蛋白表達與患者的預后無明顯關系。

引用本文： 鄭春晨,陳愉生,陳小巖,李鴻茹. Livin、Caspase-3和Bcl-2在非小細胞肺癌;的表達及生存分析. 中國呼吸與危重監護雜志, 2009, 09(3): 224-227. doi: 復制

1.	Crook NE, ClemRJ, Miller LK. An apoptosis inhibiting baculooirus gene with a zine finger like motif. J Virol, 1993, 67: 2168 -2174 .
2.	Ka H, Hunt JS. Temporal and spatial patterns of expression of inhibitors of apoptosis in human placentas. Am J Pathol, 2003, 163:413-422.
3.	Ashhab Y, Alian A, Polliack A, et al. Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distributiong pattern. FEBS Letters, 2001 , 4: 56 -60 .
4.	Gazzaniga P, Gradilone A, Giuliani L, et al. Expression and prognostic significance of Livin, Survivin and other apoptosis-related genes in the progression of superficial bladder cancer. Ann Oncol,2003, 14: 85-90.
5.	宋滔, 洪金發, 高江平, 等. 前列腺癌組織中凋亡抑制基因Livin表達研究. 中華男科學雜志, 2008, 14: 30-33.
6.	Lin JH, Deng G, Huang Q, et al. KIAP, a novel member of the inhibitor of apoptosis protein family. Biochem Biophys Res Commun, 2000, 279: 820-831.
7.	Vucic D, Stennicke HR, Pisabarro MT, et al. ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol, 2000, 10: 1359-1366.
8.	Kasof GM, Gomes BC. Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem, 2001, 276: 3238-3246.
9.	Berry N, Jones DB, Smallwood J, et al. The prognostic value of the monoclonal antibodies HMFG1 and HMFG2 in breast cancer. Br J Cancer, 1985, 51: 179-186.
10.	黎軍和, 何文靜, 和友兼. Survivin 和Livin 在Duke’B 期結直腸癌中的表達及其臨床意義. 癌癥, 2007, 26: 547-551.
11.	陶曉南, 張曉菊, 陳淼. 凋亡抑制蛋白Livin 和抑癌基因P53 在非小細胞肺癌中的表達及臨床病理學意義. 中國組織化學與細胞化學雜志, 2007, 16: 293-296.
12.	李鴻茹, 陳愉生, 陳剛, 等. Livin 在肺癌組織中的表達及與procaspase3的相關性初步探討. 中國肺癌雜志, 2007, 10: 486-490.
13.	Wang DG, Johnston CF, Sloan JM, et al. Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53. J Pathol, 1998, 184:247-251.
14.	Swanton E, Savory P, Cosulich S, et al. Bcl-2 regulates a Caspase-3 /Caspase-2 apoptotic cascade in cytosolic extracts. Oncogene, 1999 ,18: 1781-1787.
15.	Zhan Y, van de Water B, Wang Y, et al. The roles of caspase-3 andBcl-2 in chemically-induced apoptosis but not necrosis of renal epithelial cells. Oncogene, 1999, 18: 6505-6512.
16.	He H, Lam M, McCormick TS, et al. Maintenance of calcium homeostasis in the endoplasmic reticulum by Bcl-2 . J Cell Biol,1997, 138: 1219-1228.
17.	Schrantz N, Blanchard DA, Mitenne F, et al. Manganese induces apoptosis of human B cells: Caspase-dependent cell death blocked by Bcl-2. Cell Death Differ, 1999, 6: 445-453.
18.	Planchon SM, Wuerzberger-Davis SM, Pink JJ, et al. Bcl-2 protects against beta-lapachone-mediated Caspase 3 activation and apoptosis in human myeloid leukemia( HL-60) cells. Oncol Rep,1999, 6: 485-492.
19.	Nachmias B, Ashhab Y, Bucholtz V, et al. Caspase-mediated cleavage converts Livin from an antiapoptotic to a proapoptotic factor: implications for drug-resistant melanoma. Cancer Res, 2003 ,63: 6340-6349.
20.	Yoo J, Jung JH, Lee MA, et al. Immunohistochemical analysis of non-small cell lung cancer: correlation with clinical parameters and prognosis. J Korean Med Sci, 2007, 22: 318-325.
21.	Pezzella F, Turley H, Kuzu I, et al. Bcl-2 protein in non-small-cell lung carcinoma. N Engl JMed, 1993, 329: 690-694.
22.	Fontanini G, Vignati S, Bigini D, et al. Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer. Br J Cancer, 1995, 71: 1003-1007.
23.	Walker C, Robertson L, Myskow M, et al. Expression of the Bcl-2 protein in normal and dysplastic bronchial epithelium and in lung carcinomas. Br J Cancer Res, 1995, 72: 164-169.
24.	Nedelcu T, Kubista B, Koller A, et al. Livin and Bcl-2 expression in high-grade osteosarcoma. J Cancer Res Clin Oncol, 2008, 134: 237-244.
25.	Choi J, Hwang YK, Sung KW, et al. Expression of Livin, an antiapoptotic protein, is an independent favourable prognostic factor in childhood acute lymphoblastic leukemia. Blood,2007, 109:471-477.

1. Crook NE, ClemRJ, Miller LK. An apoptosis inhibiting baculooirus gene with a zine finger like motif. J Virol, 1993, 67: 2168 -2174 .
2. Ka H, Hunt JS. Temporal and spatial patterns of expression of inhibitors of apoptosis in human placentas. Am J Pathol, 2003, 163:413-422.
3. Ashhab Y, Alian A, Polliack A, et al. Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distributiong pattern. FEBS Letters, 2001 , 4: 56 -60 .
4. Gazzaniga P, Gradilone A, Giuliani L, et al. Expression and prognostic significance of Livin, Survivin and other apoptosis-related genes in the progression of superficial bladder cancer. Ann Oncol,2003, 14: 85-90.
5. 宋滔, 洪金發, 高江平, 等. 前列腺癌組織中凋亡抑制基因Livin表達研究. 中華男科學雜志, 2008, 14: 30-33.
6. Lin JH, Deng G, Huang Q, et al. KIAP, a novel member of the inhibitor of apoptosis protein family. Biochem Biophys Res Commun, 2000, 279: 820-831.
7. Vucic D, Stennicke HR, Pisabarro MT, et al. ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol, 2000, 10: 1359-1366.
8. Kasof GM, Gomes BC. Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem, 2001, 276: 3238-3246.
9. Berry N, Jones DB, Smallwood J, et al. The prognostic value of the monoclonal antibodies HMFG1 and HMFG2 in breast cancer. Br J Cancer, 1985, 51: 179-186.
10. 黎軍和, 何文靜, 和友兼. Survivin 和Livin 在Duke’B 期結直腸癌中的表達及其臨床意義. 癌癥, 2007, 26: 547-551.
11. 陶曉南, 張曉菊, 陳淼. 凋亡抑制蛋白Livin 和抑癌基因P53 在非小細胞肺癌中的表達及臨床病理學意義. 中國組織化學與細胞化學雜志, 2007, 16: 293-296.
12. 李鴻茹, 陳愉生, 陳剛, 等. Livin 在肺癌組織中的表達及與procaspase3的相關性初步探討. 中國肺癌雜志, 2007, 10: 486-490.
13. Wang DG, Johnston CF, Sloan JM, et al. Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53. J Pathol, 1998, 184:247-251.
14. Swanton E, Savory P, Cosulich S, et al. Bcl-2 regulates a Caspase-3 /Caspase-2 apoptotic cascade in cytosolic extracts. Oncogene, 1999 ,18: 1781-1787.
15. Zhan Y, van de Water B, Wang Y, et al. The roles of caspase-3 andBcl-2 in chemically-induced apoptosis but not necrosis of renal epithelial cells. Oncogene, 1999, 18: 6505-6512.
16. He H, Lam M, McCormick TS, et al. Maintenance of calcium homeostasis in the endoplasmic reticulum by Bcl-2 . J Cell Biol,1997, 138: 1219-1228.
17. Schrantz N, Blanchard DA, Mitenne F, et al. Manganese induces apoptosis of human B cells: Caspase-dependent cell death blocked by Bcl-2. Cell Death Differ, 1999, 6: 445-453.
18. Planchon SM, Wuerzberger-Davis SM, Pink JJ, et al. Bcl-2 protects against beta-lapachone-mediated Caspase 3 activation and apoptosis in human myeloid leukemia( HL-60) cells. Oncol Rep,1999, 6: 485-492.
19. Nachmias B, Ashhab Y, Bucholtz V, et al. Caspase-mediated cleavage converts Livin from an antiapoptotic to a proapoptotic factor: implications for drug-resistant melanoma. Cancer Res, 2003 ,63: 6340-6349.
20. Yoo J, Jung JH, Lee MA, et al. Immunohistochemical analysis of non-small cell lung cancer: correlation with clinical parameters and prognosis. J Korean Med Sci, 2007, 22: 318-325.
21. Pezzella F, Turley H, Kuzu I, et al. Bcl-2 protein in non-small-cell lung carcinoma. N Engl JMed, 1993, 329: 690-694.
22. Fontanini G, Vignati S, Bigini D, et al. Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer. Br J Cancer, 1995, 71: 1003-1007.
23. Walker C, Robertson L, Myskow M, et al. Expression of the Bcl-2 protein in normal and dysplastic bronchial epithelium and in lung carcinomas. Br J Cancer Res, 1995, 72: 164-169.
24. Nedelcu T, Kubista B, Koller A, et al. Livin and Bcl-2 expression in high-grade osteosarcoma. J Cancer Res Clin Oncol, 2008, 134: 237-244.
25. Choi J, Hwang YK, Sung KW, et al. Expression of Livin, an antiapoptotic protein, is an independent favourable prognostic factor in childhood acute lymphoblastic leukemia. Blood,2007, 109:471-477.

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《中國呼吸與危重監護雜志》

Livin、Caspase-3和Bcl-2在非小細胞肺癌;的表達及生存分析

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