Expression And Significance Of Livin And Smac In Renal Cell Carcinoma Tissues

Background and Objective Livin is one of the members of human inhibitor of apoptosis proteins(lAPs) family.Its central mechanism is direct or indirect inhibition of Caspase-3 and Caspase-7,the terminal effectors of apoptotic pathway.Smac(Second mitochondrial-derived activator of Caspase,Smac) is the first mammalian RHG protein to be described,and many studies have demonstrated that it can inhibit lAPs by direct binding.In the intrinsic cell death pathway,it is released from the intermembrane space of mitochondria into the cytosol with cyto-c,and binds to a highly conserved surface groove on the BIR domain of lAPs,then inhibiting lAP-mediated apoptosis.The report about correlation of the expressions of Livin and Smac in renal clear cell carcinoma(RCCC) is not found by now.This study is to investigate the expressions of Livin and Smac and their relationship in RCCC,and to explore a safe surgical margin of nephron sparing surgery.Material and Method RCCC specimens with full clinicopathological data were selected and confirmed by the postoperative pathologic diagnosis.There were 30 men and 19 women,age from 29 to 82 years old,and mean age of 42.7 years old.Pathological grade(according to WHO of 1997):high,12 cases;moderate,26 cases;low(no),11 cases. The clinical stage was divided according to the standard of AJCC(2002):stage 1,21 cases;staeⅡ,13 cases;stageⅢ,10 cases;stageⅣ,5 cases.There were 12 cases with lymph node metastasis and 37 cases without.Twenty cases of non renal carcinoma tissues were studied as control.The expressions of Livin and Smac in RCCC and normal renal tissues were detected by using reverse transcription-polymerase chain reaction(RT-PCR),and both genes were also detected in cancer-adjacent 0 to 0.5 cm and cancer-adjacent more than 1 cm of PT1a renal clear cell carcinoma.All data were tested byχ~2-test or Spearman rank correlation test(P＜0.05 was considered statistical significance).Results1.The expression of Livin in RCCC and normal renal tissues.The Livin positive expression rate in RCCC was 79.6%(39/49),and it was 20.0% (4/20) in normal renal tissues.The difference was significant(χ~2=21.479,P＜0.05).In RCCC,the expression rate of Livin in high/middle and low/no histological differentiation groups were 73.7%(28/38)and 100.0%(11/11),however,there was no statistical significance between them(χ~2=3.637,P＞0.05).Livin total positive rate was 70.6%(24/34) in stagesⅠ/Ⅱand 100.0%(15/15)in stageⅢ/Ⅳ;there was statistical significance between them(χ~2=5.543,P＜0.05).Livin positive rate was 100.0%(12/12) in patients with lymph node metastasis and 73.0%(27/37) in those without;there was significant association between expression of Livin and metastasis(χ~2=4.75,P＜0.05).2.The expression of Smac in RCCC and normal renal tissues.The Smac positive expression rate in RCCC was 75.5%(37/49),and 20 cases of normal renal tissues were all positive.The difference was significant(χ~2=5.929,P＜0.05).In RCCC,the expression rate of Smac in high/middle and low/no histological differentiation groups were 89.5%(34/38) and 27.3%(3/11);there was statistical significance between them(χ~2=17.848,P＜0.05).Smac total positive rate was 91.2%(31/34) in stagesⅠ/Ⅱ,and 40.0%(6/15) in stageⅢ/Ⅳ;there was statistical significance between them(χ~2=14.741,P＜0.05).Smac positive rate in patients with lymph node metastasis was 33.3%(4/12)and 89.2%(33/37)in those without;there was significant association between expression of Smac and metastasis(χ~2= 15.287,P＜0.05).3.There was a negative correlation between the expression of Livin and Smac in RCCC (r_s=-0.39,P＜0.05).4.In PT1a of RCCC,the Livin expression rate in cancer center and cancer-adjacent 0 to 0.5 cm were both 75.0%(12/16),and it was 18.8%(3/16) in cancer-adjacent more than 1 cm;the difference was significant(χ~2=10.165,P＜0.05).The difference of Smac expression rate in cancer center,cancer-adjacent 0 to 0.5 cm and cancer-adjacent more than 1 cm was not signficant(χ~2=1.032,P＞0.05).Conclusion In this study we found that the expression rate of Livin was high and Smac was low in RCCC;moreover,the expression of Livin was positively correlated to clinical stage and lymph node metastasis in RCCC,but the expression of Smac was negatively correlated to the degree of malignancy,clinical stage and lymph node metastasis in RCCC.It was indicated that there was an intimate relationship between Livin, Smac and RCC genesis and development.There was a negative correlation between the expression of Livin and Smac in RCCC. It suggested that Livin and Smac play antagonistic roles in cancer cell apoptosis. Decreasing the expression of Smac might indirectly or directly cause Livin over-express, or the over-expression of Livin inhibited cell apoptosis and promoted aberrant proliferation and malignant transformation of the cells.The relationship between Livin and Smac may play a central role in carcinogenesis of RCC.Surgical margin(1cm) far from the outer edge of tumor was safe when PT1a RCCC patient was undergone nephron sparing surgery by the expression of Livin.