Abstract
BackgroundEpithelial-mesenchymal transition (EMT) is involved in important malignant features of cancer cells, like invasion, metastatic potential, anti-apoptotic and stem-cell like phenotypes. Among several transcription factors, SNAI2/SLUG is supposed to play an essential role for EMT.MethodsParaffin embedded tumor samples from 63 patients with metastatic non-small cell lung cancer, enrolled in a randomized phase II trial, were prospectively collected, 53 samples qualified for further analysis. Automated RNA extraction from paraffin and RT-quantitative PCR was used for evaluation of SNAI2/SLUG, estrogen receptor 1 (ESR1) and matrix-metalloproteinases (MMP) mRNA expression.ResultsClinical features like age, gender, performance status, histological subtype and stage were similarly distributed among SNAI2/SLUG positive and negative patients. SNAI2/SLUG was significantly, inversely correlated with ESR1 mRNA expression (p < 0.0001). In contrast, MMP2 (p = 0.387), MMP7 (p = 0.396) and MMP9 mRNA expression (p = 0.366) did not correlate with SNAI2/SLUG. Patients with high SNAI2/SLUG expression (grouped by median expression) had a worse outcome. Median overall survival in patients with high SNAI2/SLUG expression was 5.7 months versus 11.6 months with low SNAI2/SLUG expression (p = .038). Inversely, patients with high ESR1 expression (grouped by median expression) had an improved median OS with 10.9 months vs. 5.0 months in the low expression group (p = .032). In multivariate analysis, SNAI2/SLUG2 (p = .022) and ESR1 (p = .017) separately were independent prognostic factors for survival.ConclusionSNAI2/SLUG is prognostic of patients’ outcome. The strong inverse correlation with ESR1 indicates a significant impact of estrogen receptor pathway regarding these malignant features.
Highlights
Epithelial-mesenchymal transition (EMT) is involved in important malignant features of cancer cells, like invasion, metastatic potential, anti-apoptotic and stem-cell like phenotypes
Several findings of this study indicate that SNAI2/SLUG is an estradiol- responsive gene and estrogen receptor α (ERα) may play an important role in EMT in breast cancer
SNAI2/SLUG and MMP mRNA expression SNAI2/SLUG mRNA expression could be evaluated in 49 patients and ranged between 28.01 and 41.70 with a median of 34.09 (ΔCt)
Summary
Epithelial-mesenchymal transition (EMT) is involved in important malignant features of cancer cells, like invasion, metastatic potential, anti-apoptotic and stem-cell like phenotypes. Atmaca et al BMC Cancer (2015) 15:300 matix-metalloproteinases (MMP), can be observed, contributing to the increase of cell motility, invasiveness and metastatic potential [1,2]. Overexpression of SNAI2/SLUG can be observed in a variety of different cancers and seems to be associated with poor outcome [4,5]. SNAI2/SLUG is a negative prognostic factor for relapse and overall survival in resectable, early stage lung cancer [6,7]. Several findings of this study indicate that SNAI2/SLUG is an estradiol- responsive gene and ERα may play an important role in EMT in breast cancer
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