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


CONCLUSIONS
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.
Department of Hematology and Oncology, Krankenhaus Nordwest, UCT-University Cancer Center, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany. atmaca.akin@khnw.de.
Akin
A
Atmaca
STRATIFYER Molecular Pathology GmbH, Werthmannstraße 1, 50935, Cologne, Germany. ralph.wirtz@stratifyer.de.
Ralph W
RW
Wirtz
Institute of clinical research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany. dominiquewerner@arcor.de.
Dominique
D
Werner
Institute of clinical research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany. steinmetz.kristina@khnw.de.
Kristina
K
Steinmetz
STRATIFYER Molecular Pathology GmbH, Werthmannstraße 1, 50935, Cologne, Germany. silke.claas@stratifyer.de.
Silke
S
Claas
Department of Internal Medicine 3, Klinikum Nürnberg, Prof.-Ernst-Nathan-Straße 1, 90419, Nuermberg, Germany. Wolfgang.Brueckl@klinikum-nuernberg.de.
Wolfgang M
WM
Brueckl
Department of Hematology and Oncology, Krankenhaus Nordwest, UCT-University Cancer Center, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany. jaeger.elke@khnw.de.
Elke
E
Jäger
Institute of clinical research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany. albatran.salah@khnw.de.
Salah-Eddin
SE
Al-Batran
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors