Valdés-Mora Fátima, Gómez del Pulgar Teresa, Bandrés Eva, Cejas Paloma, Ramírez de Molina Ana, Pérez-Palacios Rosa, Gallego-Ortega David, García-Cabezas Miguel Angel, Casado Enrique, Larrauri Javier, Nistal Manuel, González-Barón Manuel, García-Foncillas Jesús, Lacal Juan Carlos
Centro Nacional de Biotecnología, C/ Darwin, 3. Campus Cantoblanco, 28049, Madrid, Spain.
Ann Surg Oncol. 2009 Jan;16(1):78-87. doi: 10.1245/s10434-008-0166-x. Epub 2008 Nov 11.
TWIST1 is a basic helix-loop-helix (bHLH) transcription factor that has been involved in tumor progression and metastasis in several cancer types, although no evidence has been provided yet on its implication in colorectal carcinogenesis.
We examined the expression pattern of TWIST1 messenger RNA (mRNA) in 54 colorectal cancer biopsies compared with each respective adjacent normal mucosa by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) methodology.
TWIST1 mRNA was found significantly overexpressed in colorectal cancer samples compared to nontumorous colon mucosa (P < 0.0001). Receiver operating characteristic (ROC) curve analysis demonstrated that TWIST1 mRNA levels are significantly increased in patients with nodal invasion and, interestingly, a significant correlation with patient sex was also found.
Evidence for upregulation of TWIST1 mRNA in colorectal cancer is provided, suggesting its implication in the onset of malignant progression of this disease. In addition, significant higher levels of TWIST1 mRNA were found in men than in women, suggesting a possible transcriptional regulation of TWIST1 by sexual hormones. The use of TWIST1 as a new prognostic marker of advanced malignancy, and as a potential therapeutic target in colorectal cancer, is proposed.
TWIST1是一种碱性螺旋-环-螺旋(bHLH)转录因子,已参与多种癌症类型的肿瘤进展和转移,尽管尚未有证据表明其与结直肠癌发生有关。
我们采用实时逆转录聚合酶链反应(RT-PCR)方法,检测了54例结直肠癌活检组织中TWIST1信使核糖核酸(mRNA)的表达模式,并与各自相邻的正常黏膜进行比较。
与非肿瘤性结肠黏膜相比,结直肠癌样本中TWIST1 mRNA显著过表达(P < 0.0001)。受试者工作特征(ROC)曲线分析表明,TWIST1 mRNA水平在有淋巴结转移的患者中显著升高,有趣的是,还发现其与患者性别存在显著相关性。
本研究提供了结直肠癌中TWIST1 mRNA上调的证据,提示其与该疾病恶性进展的起始有关。此外,男性的TWIST1 mRNA水平显著高于女性,提示性激素可能对TWIST1有转录调控作用。我们建议将TWIST1用作晚期恶性肿瘤的新预后标志物以及结直肠癌的潜在治疗靶点。