Atmaca Akin, Wirtz Ralph W, Werner Dominique, Steinmetz Kristina, Claas Silke, Brueckl Wolfgang M, Jäger Elke, Al-Batran Salah-Eddin
Department of Hematology and Oncology, Krankenhaus Nordwest, UCT-University Cancer Center, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany.
STRATIFYER Molecular Pathology GmbH, Werthmannstraße 1, 50935, Cologne, Germany.
BMC Cancer. 2015 Apr 17;15:300. doi: 10.1186/s12885-015-1310-1.
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.
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.
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.
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.
上皮-间质转化（EMT）与癌细胞的重要恶性特征有关，如侵袭、转移潜能、抗凋亡和干细胞样表型。在几种转录因子中，SNAI2/SLUG被认为在EMT中起关键作用。
前瞻性收集了63例转移性非小细胞肺癌患者的石蜡包埋肿瘤样本，这些患者参加了一项随机II期试验，53个样本符合进一步分析的条件。采用从石蜡中自动提取RNA和逆转录定量PCR技术评估SNAI2/SLUG、雌激素受体1（ESR1）和基质金属蛋白酶（MMP）mRNA的表达。
SNAI2/SLUG阳性和阴性患者的年龄、性别、体能状态、组织学亚型和分期等临床特征分布相似。SNAI2/SLUG与ESR1 mRNA表达呈显著负相关（p < 0.0001）。相反，MMP2（p = 0.387）、MMP7（p = 0.396）和MMP9 mRNA表达（p = 0.366）与SNAI2/SLUG无关。SNAI2/SLUG高表达患者（按中位表达分组）预后较差。SNAI2/SLUG高表达患者的中位总生存期为5.7个月，而SNAI2/SLUG低表达患者为11.6个月（p = 0.038）。相反，ESR1高表达患者（按中位表达分组）的中位总生存期有所改善，高表达组为10.9个月，低表达组为5.0个月（p = 0.032）。在多变量分析中，SNAI2/SLUG2（p = 0.022）和ESR1（p = 0.017）分别是生存的独立预后因素。
SNAI2/SLUG可预测患者的预后。与ESR1的强负相关表明雌激素受体途径对这些恶性特征有显著影响。
