Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Ann Surg Oncol. 2012 Mar;19(3):743-9. doi: 10.1245/s10434-011-2074-8. Epub 2011 Oct 18.
Epithelial-mesenchymal transition has recently attracted great attention in studying the malignant progression of cells through a converging pathway of oncogenesis and metastasis. Twist1 and Mastermind-like 1 (MAML1) are major regulators of EMT through different pathways. The aim of this study was to investigate the clinicopathological relevance of the expression of MAML-1 and Twist1 genes in esophageal squamous cell carcinoma (ESCC).
Tumoral and corresponding normal tissues from 55 treatment-naive ESCC patients were subjected for expression analysis with quantitative real-time RT-PCR.
Overexpression of MAML-1 and Twist1 were significantly associated with lymph node metastasis and the surgical staging of tumor. Overexpression of Twist1 was associated with tumor depth of invasion. Mean relative expression (MRE) of MAML1 was significantly higher in patients with metastasis to lymph nodes (3.07 ± 0.51 vs. 0.86 ± 0.58, P = .008). MRE of Twist1 was significantly higher in patients with invasion of tumor to adventitia (T3, T4) (1.97 ± 0.29 vs. 0.39 ± 0.73, P = .036). In advanced stages of tumor (stage III, IV), a significantly higher MRE of Twist1 (2.47 ± 0.41 vs. 1.25 ± 0.36, P = .035) and MAML1 (3.05 ± 0.45 vs. 1.07 ± 0.59, P = .021) mRNA was observed.
We introduce Twist1 and MAML1 as new molecular markers of advanced tumor, which determine the characteristics and aggressive behavior of ESCC. Along with the emerging evidence of their role in different cellular processes and aberrations in various cancers, they are suggested as potentially interesting therapeutic targets to reverse a broad spectrum of functional aberrations that promote ESCC development.
上皮-间充质转化最近引起了人们对通过致癌和转移的汇聚途径研究细胞恶性进展的极大关注。 Twist1 和 Mastermind-like 1(MAML1)是 EMT 的主要调节因子,通过不同的途径。本研究旨在探讨 MAML-1 和 Twist1 基因在食管鳞状细胞癌(ESCC)中的表达与临床病理的相关性。
对 55 例未经治疗的 ESCC 患者的肿瘤和相应的正常组织进行定量实时 RT-PCR 表达分析。
Twist1 和 MAML1 的过表达与淋巴结转移和肿瘤的手术分期显著相关。 Twist1 的过表达与肿瘤浸润深度有关。有淋巴结转移的患者 MAML1 的平均相对表达(MRE)明显较高(3.07±0.51 对 0.86±0.58,P=.008)。肿瘤侵犯外膜(T3、T4)的患者 Twist1 的 MRE 明显较高(1.97±0.29 对 0.39±0.73,P=.036)。在肿瘤的晚期(III 期、IV 期), Twist1(2.47±0.41 对 1.25±0.36,P=.035)和 MAML1(3.05±0.45 对 1.07±0.59,P=.021)的 MRE 明显较高。
我们将 Twist1 和 MAML1 作为肿瘤晚期的新分子标志物引入,它们决定了 ESCC 的特征和侵袭行为。随着它们在不同细胞过程中的作用以及在各种癌症中异常的出现证据不断增加,它们被认为是潜在的有意义的治疗靶点,可以逆转促进 ESCC 发展的广泛功能异常。