Background: Survivin is an anti-apoptotic protein and is considered as one of the principle inhibitors of apoptosis (IAP) family which has shown its role in cancer progression, tumor angiogenesis, tumor resistance to chemotherapeutics and radiation. Our goal was to prove the importance of survivin in NSCLC patients and to evaluate if the peripheral blood (PB) survivin level is as prognostic as tissue survivin over expression.
Methods: We enrolled Non-small cell lung cancer patients in the advanced stage prospectively from (2015 to 2017). Real-time PCR was done to detect survivin expression in the blood. Determination of survival time, time to progression of the disease (TTP) and progression free survival (PFS) were the primary outcomes while the other outcomes were to identify the associations between different variables and survivin cutoff, determined by (ROC) curve. Mann Whitney-U and Chi (X2 ) were used. To estimate the survival, Kaplan-Meier curves were used and compared using Log-rank. Cox regression was included to identify if survivin was a predictor of survival.
Results: Sixty-six patients with a median age of 55 years (range 47-63.3), 25.8% were females. Adenocarcinoma represented 59.1%. Twelve cases developed progressive disease (PD) among them eight cases had bone metastasis. Median OS, TTP and PFS was 17.1 months (95% CI 13.1-20.9), 11.0 (95% CI 7.3-14.8) and 8.9 (95% CI 8.1-9.8) respectively. The chosen cutoff point for blood survivin level was 3.8 pg/ml (Area under ROC curve=0.644 (95%CI=0.51-0.78), P=0.044) that was associated with better median TTP and PFS of 12.0 vs. 4.9 months and 9.0 vs. 4.9 months in low survivin (≤ 3.8 pg/ml) versus high (>3.8 pg/ml) group (P=0.001 and 0.006) respectively. High Survivin group (>3.8 pg/ml) was associated with worse TTP (Hazard ratio (HR 5.66 (95% CI 1.8-17.7; P=0.003)) and more common to have bone metastasis after PD (100% vs. 26.3% in low survivin (P=0.014).
Conclusion: Survivin is a significant predictor of TTP and PFS in advanced non squamous lung cancer patients. Metastasis is less common in the low survivin group.
Reham A Rashed, Mohamed Rahouma, Mahmoud Morsi, Rasha Allam, Randa M. Abo Elfetouh and Hala Aziz