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SNAI2/SLUG and estrogen receptor mRNA expression are inversely correlated and prognostic of patient outcome in metastatic non-small cell lung cancer.

Atmaca A, Wirtz RW, Werner D, Steinmetz K, Claas S, Brueckl WM, Jäger E, Al-Batran SE - BMC Cancer (2015)

Bottom Line: 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.SNAI2/SLUG is prognostic of patients' outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Krankenhaus Nordwest, UCT-University Cancer Center, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany. atmaca.akin@khnw.de.

ABSTRACT

Background: Epithelial-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.

Methods: Paraffin 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.

Results: Clinical 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.

Conclusion: SNAI2/SLUG is prognostic of patients' outcome. The strong inverse correlation with ESR1 indicates a significant impact of estrogen receptor pathway regarding these malignant features.

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Related in: MedlinePlus

Kaplan-Meier curves for overall survival (OS) grouped by median SLUG/SNAI2 expression (A) and by 3rd quartile of SLUG/SNAI2 expression (B) for patients with SLUG/SNAI2 high and low tumors. A: median OS (median SLUG/SNAI2 expression): 5.7 vs. 11.6 months, p = 0.038, HR 0.52. B: median OS (3rd quartile): 4.6 vs. 11.5 months, p = 0.0192, HR 0.45.
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Fig1: Kaplan-Meier curves for overall survival (OS) grouped by median SLUG/SNAI2 expression (A) and by 3rd quartile of SLUG/SNAI2 expression (B) for patients with SLUG/SNAI2 high and low tumors. A: median OS (median SLUG/SNAI2 expression): 5.7 vs. 11.6 months, p = 0.038, HR 0.52. B: median OS (3rd quartile): 4.6 vs. 11.5 months, p = 0.0192, HR 0.45.

Mentions: In line with previous works of our group [11], ESR1 expression was identified as a marker of favourable outcome in this patient group (n = 53) with a median OS of 10.9 vs. 5.0 months in ESR1 high vs. low patients, respectively (p = .032, HR 0.51). Grouped by the median SNAI2/SLUG expression, OS was 5.7 vs. 11.6 months in the SNAI2/SLUG high vs. low patients (p = .038, HR 0.52) (Figure 1A). When the 3rd quartile of SNAI2/SLUG expression (37.75) was used for classification into high vs. low patients, the differences in OS were even stronger (median OS 4.6 vs 11.5 months, p = .0192, HR 0.45) (Figure 1B).Figure 1


SNAI2/SLUG and estrogen receptor mRNA expression are inversely correlated and prognostic of patient outcome in metastatic non-small cell lung cancer.

Atmaca A, Wirtz RW, Werner D, Steinmetz K, Claas S, Brueckl WM, Jäger E, Al-Batran SE - BMC Cancer (2015)

Kaplan-Meier curves for overall survival (OS) grouped by median SLUG/SNAI2 expression (A) and by 3rd quartile of SLUG/SNAI2 expression (B) for patients with SLUG/SNAI2 high and low tumors. A: median OS (median SLUG/SNAI2 expression): 5.7 vs. 11.6 months, p = 0.038, HR 0.52. B: median OS (3rd quartile): 4.6 vs. 11.5 months, p = 0.0192, HR 0.45.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4404179&req=5

Fig1: Kaplan-Meier curves for overall survival (OS) grouped by median SLUG/SNAI2 expression (A) and by 3rd quartile of SLUG/SNAI2 expression (B) for patients with SLUG/SNAI2 high and low tumors. A: median OS (median SLUG/SNAI2 expression): 5.7 vs. 11.6 months, p = 0.038, HR 0.52. B: median OS (3rd quartile): 4.6 vs. 11.5 months, p = 0.0192, HR 0.45.
Mentions: In line with previous works of our group [11], ESR1 expression was identified as a marker of favourable outcome in this patient group (n = 53) with a median OS of 10.9 vs. 5.0 months in ESR1 high vs. low patients, respectively (p = .032, HR 0.51). Grouped by the median SNAI2/SLUG expression, OS was 5.7 vs. 11.6 months in the SNAI2/SLUG high vs. low patients (p = .038, HR 0.52) (Figure 1A). When the 3rd quartile of SNAI2/SLUG expression (37.75) was used for classification into high vs. low patients, the differences in OS were even stronger (median OS 4.6 vs 11.5 months, p = .0192, HR 0.45) (Figure 1B).Figure 1

Bottom Line: 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.SNAI2/SLUG is prognostic of patients' outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Krankenhaus Nordwest, UCT-University Cancer Center, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany. atmaca.akin@khnw.de.

ABSTRACT

Background: Epithelial-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.

Methods: Paraffin 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.

Results: Clinical 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.

Conclusion: SNAI2/SLUG is prognostic of patients' outcome. The strong inverse correlation with ESR1 indicates a significant impact of estrogen receptor pathway regarding these malignant features.

Show MeSH
Related in: MedlinePlus