Journal
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
Volume 54, Issue 2, Pages 237-245Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/ejcts/ezy022
Keywords
Epithelial-mesenchymal transition; Lung cancer; Prognosis; Immunohistochemistry
Funding
- Provincial Science and Technology Development Plan of Shandong [2015GSF118063]
- National Science Foundation of China [81602009]
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OBJECTIVES: Lung cancer is the leading cause of cancer-related death worldwide. The 5-year survival rate for patients after curative surgery with pathological NO non-small-cell lung cancer (NSCLC) is as low as 56%, which is due to recurrence and metastasis. Emerging evidence suggests that epithelial-mesenchymal transition is important for cancer metastasis. Twist and Snail are epithelial-mesenchymal transition regulators that induce metastasis by down-regulating E-cadherin. The aim of this study was to evaluate the prognostic value of Twist, Snail and E-cadherin expression in patients with resectable pathological NO NSCLC. METHODS: The expression levels of Twist Snail and E-cadherin in 78 patients with resected pathological NO NSCLC were assessed using immunohistochemistry. The association between the expression of Twist/Snail/E-cadherin and overall survival (OS) and recurrence-free survival (RFS) was investigated. RESULTS: High expression of Twist, Snail and E-cadherin was detected in 18%, 21% and 53% of NSCLC samples, respectively. High expression of Twist and Snail and low expression of E-cadherin were associated with worse RFS [hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.07-4.87, P = 0.026; HR 2.54, 95% CI 1.24-5.20, P = 0.008 and HR 2.41, 95% CI 1.23-4.73, P = 0.007, respectively] and worse OS (HR 2.26, 95% CI 1.01-5.04, P = 0.040; HR 2.56, 95% CI 1.20-5.43, P = 0.011 and HR 2.42, 95% CI 1.18-4.95, P = 0.012, respectively). Coexpression of at least 2 markers from the combination of high Twist/high Snail/low E-cadherin expression predicted poor RFS and OS (HR 4.12, 95% CI 2.08-8.16, P < 0.001 and HR 4.28, 95% CI 2.08-8.77, P < 0.001, respectively), and it was an independent predictor of RFS and OS (HR 3.99, 95% CI 1.89-8.44, P < 0.001 and HR 4.16, 95% CI 1.88-9.18, P < 0.001, respectively). CONCLUSIONS: Co-expression of at least 2 markers from the combination of high Twist/high Snail/low E-cadherin expression was a significant prognostic predictor in patients with pathological NO NSCLC.
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