Expression Of Survivin In Human Non-small Cell Lung Cancer And Its Association With COX-2 And Apoptosis

Objective This study aimed at investigating survivin expression and cyclooxygenase-2 (GOX-2) expression in human non-small cell lung cancer (NSCLC) and their association, exploring their relation with apoptosis, and analyzing their significance on prognosis estimation.Methods Survivin expression and COX-2 expression were evaluated immunohistochemically in 75 NSCLC and 30 normal lung specimens. TUNEL was employed to detect apoptosis in situ.Results Survivin expression and COX-2 expression were in a significantly greater proportion in NSCLC specimens (70.6% and 68.0%) than those in normal lung specimens (6.7% and 10.0%) (Fisher's exact test, both p<0.05). Survivin was negatively related to apoptotic index (AI) (Spearman's correlation, r=-0.86, p<0.05) and COX-2 was negativelyrelated to AI (Spearman's correlation, r=-0.75, p<0.05). Survivin was positively related to COX-2 (Spearman's correlation, r=0.78, p<0.05). AI in survivin-positive subgroup was lower than that in survivin-negative subgroup (Wicoxon test, z=5.10, p<0.0001). AI in COX-2-positive subgroup was lower than that in COX-2-negative subgroup (Wicoxon test, z=5.36, p<0.0001). Survivin positivity and COX-2 positivity in stage III subgroup (84.4%, 90.9, respectively) were significantly greater than those in stage I~II subgroup (50.9%, 50.0%, respectively) (Chi-square test,x~2=4.56, p=0.03, x~2 =12.4, p=0.004, respectively). Survivin positivity and COX-2 positivity in low differentiated subgroup (83.3%, 86.7%, respectively) were significantly greater than those in well differentiatedsubgroup (53.8%, 50.0%, respectively) (Chi-square test, x~2=12.40, p=0.0004, x~2 =7.21, p=0.0007, respectively). Survival analysis employing Kaplan-Meier method indicated five-year survival rate in survivin-negative subgroup (28.6%) was greater than that insurvivin-positive subgroup (8.5%) (Log rank test, x~2 =14.3, p=0.0002); and five-year survival rate in COX-2-negative subgroup (21.7%) was greater than that in COX-2-positive subgroup (11.1%) (Log rank test,x~2=9.4, p=0.002). Multivariate analysis employing COX proportionalhazard model showed that survivin expression (x~2=41.4 p<0.0001, hazard ratio=1.296, partial regression coefficient=0.25948) and TNM stage( x~2 =11.4, p=0.0007, hazard ratio=1.387, partial regressioncoefficient=0.72739) were the factors which predicted increased risk of death.Conclusions Survivin expression and COX-2 were increased in NSCLC, and survivin positively correlated with COX-2. Both survivin and COX-2 was negatively correlated with AI. The exact interaction between survivin and COX-2 remains to be elucidated. Survivin and COX-2 may play an important role in the pathway of carcinogenesis and progression of NSCLC and associate with the malignancy of NSCLC. Up-regulation of survivin expression predicts poorer prognosis in NSCLC.