Survivin is a protein that inhibits apoptosis and has been shown its role in cancer progression, tumor angiogenesis, tumor cell resistance to chemotherapeutics and ionizing radiation. We aimed to evaluate the importance of survivin in lung cancer patients and identify its role in disease progression and outcome.
We prospectively enrolled advanced non-small cell lung cancer (NSCLC) patients (2015-2017). Serum survivin expression levels were detected in the peripheral blood using real-time RT-PCR. The primary outcomes were to identify overall survival (OS), progression free survival (PFS) and time to progression (TTP) while the secondary outcomes were to identify the associations between different variables and survivin cut-off determined by receiver operating characteristic (ROC) curve. Chi(X2) and Mann Whitney-U tests were used. Kaplan-Meier survival curves were used and compared using Log-rank. Cox regression was used to identify if survivin was a predictor of survival.
66 patients were recruited with median age of 55 years (Inter-quartile range: 47- 63.3), 74.2% were males. Adenocarcinoma represented 59.1%. 12 cases developed progressive disease (PD) with 8 cases had bone metastasis after PD. 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. Chosen cut-off for survivin was 3.80 (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 vs high (>3.8) groups (P = 0.001 and 0.006) respectively. Survivin >3.80 was associated with worse TTP (Hazard ratio (HR) 5.66 (95%CI 1.8-17.7; P = 0.003). Higher survivin was associated with bone metastasis after PD (100% vs 26.3 in low survivin (P = 0.014).
Survivin is a significant predictors of time to progression and progression free survival in advanced NSCLC. Bone metastasis is common in high survivin group. CI: 95% confidence interval, NR: not reached, OS: overall survival, PFS: progression free survival, TTP: time to progressionKaplan Meier survival curves estimated median survival (in months) for survivin subgroups (≤3.80 vs > 3.80): A) overall survival (OS), B) time to progression (TP) and C) progression free survival (PFS) Median survival (months) Lower CI Upper CI P-value OS (overall) 17.063 13.140 20.986 - Survivin ≤3.80 17.063 0.156 - Survivin >3.80 NR TTP (overall) 11.047 7.327 14.766 ------ - Survivin ≤3.80 12.000 0.001 - Survivin >3.80 4.964 PFS (overall) 8.975 8.149 9.802 ------ - Survivin ≤3.80 9.041 0.006 - Survivin >3.80 4.964
The authors.
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All authors have declared no conflicts of interest.