High TWIST1 mRNA expression is associated with poor prognosis in lymph node-negative and estrogen receptor-positive human breast cancer and is co-expressed with stromal as well as ECM related genes.
High TWIST1 mRNA expression is associated with poor prognosis in lymph node-negative and estrogen receptor-positive human breast cancer and is co-expressed with stromal as well as ECM related genes.
复制标题
DOI：
10.1186/bcr3317
复制
发表时间：
2012-09-11
期刊：
影响因子：
--
通讯作者：
Martens JW
中科院分区：
文献类型：
--
作者：
Riaz M;Sieuwerts AM;Look MP;Timmermans MA;Smid M;Foekens JA;Martens JW
TWIST同源物1（TWIST 1）是诱导上皮向间质转化（EMT）的转录因子，EMT是转移的关键过程。本研究的目的是调查TWIST 1表达是否预测长期临床随访的大型乳腺癌队列中的疾病进展，并揭示与TWIST 1介导的疾病进展相关的生物学。通过实时定量逆转录聚合酶链反应（RT-PCR）分析了1，427例原发性乳腺癌中TWIST 1 mRNA的表达水平。在单因素和多因素分析中，使用考克斯回归，TWIST 1 mRNA表达水平与无转移生存期（MFS），无病生存期（DFS）和总生存期（OS）。在分层为雌激素受体（ER）阳性（n = 552）和ER阴性（n = 226）疾病之前和之后，还对未接受辅助全身治疗的淋巴结阴性患者（LNN，n = 778）进行了单独分析。使用Kaplan-Meier分析评估TWIST 1 mRNA与生存终点的相关性。使用基因表达阵列，显示与TWIST 1显著斯皮尔曼等级相关的基因用于鉴定过度代表的基因本体论（GO）术语和京都基因和基因组百科全书（KEGG）注释的生物途径。在单因素和多因素分析中，TWIST 1 mRNA表达水平的增加作为一个连续变量，与所有患者的MFS缩短相关（风险比（HR）：1.17，95%置信区间，（95% CI）：1.09 - 1.26; HR：1.17，95% CI：1.08 - 1.26），LNN患者（HR：1.22，95%CI：1.09 - 1.36;和HR：1.21，95%CI：1.07 - 1.36;分别）和ER阳性LNN患者亚组（HR：1.34，95%CI：1.17 - 1.53;和HR：1.32，95%CI：1.14 - 1.53;分别）。同样，在所有患者和LNN/ER阳性亚组中，TWIST 1高表达与较短的DFS和OS相关。相反，在ER阴性患者中，TWIST 1 mRNA表达与MFS、DFS或OS无关。与TWIST 1高度相关的基因在细胞粘附和ECM相关信号通路中显著富集。TWIST 1 mRNA在肿瘤间质中呈高表达，且与肿瘤间质含量呈正相关（P <0.001）。TWIST 1 mRNA表达是LNN/ER阳性乳腺癌预后不良的独立预后因素。生物学关联表明肿瘤微环境参与了TWIST 1在乳腺癌中的不利作用。
The TWIST homolog 1 (TWIST1) is a transcription factor that induces epithelial to mesenchymal transition (EMT), a key process in metastasis. The purpose of this study was to investigate whether TWIST1 expression predicts disease progression in a large breast cancer cohort with long-term clinical follow-up, and to reveal the biology related to TWIST1 mediated disease progression. TWIST1 mRNA expression level was analyzed by quantitative real-time reverse polymerase chain reaction (RT-PCR) in 1,427 primary breast cancers. In uni- and multivariate analysis using Cox regression, TWIST1 mRNA expression level was associated with metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS). Separate analyses in lymph node-negative patients (LNN, n = 778) who did not receive adjuvant systemic therapy, before and after stratification into estrogen receptor (ER)-positive (n = 552) and ER-negative (n = 226) disease, were also performed. The association of TWIST1 mRNA with survival endpoints was assessed using Kaplan-Meier analysis. Using gene expression arrays, genes showing a significant Spearman rank correlation with TWIST1 were used to identify overrepresented Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG)-annotated biological pathways. Increased mRNA expression level of TWIST1 analyzed as a continuous variable in both uni- and multivariate analysis was associated with shorter MFS in all patients (hazard ratio (HR): 1.17, 95% confidence interval, (95% CI):1.09 to 1.26; and HR: 1.17, 95% CI: 1.08 to 1.26; respectively), in LNN patients (HR: 1.22, 95% CI: 1.09 to 1.36; and HR: 1.21, 95% CI: 1.07 to 1.36; respectively) and in the ER-positive subgroup of LNN patients (HR: 1.34, 95% CI: 1.17 to 1.53; and HR: 1.32, 95% CI: 1.14 to 1.53; respectively). Similarly, high TWIST1 expression was associated with shorter DFS and OS in all patients and in the LNN/ER-positive subgroup. In contrast, no association of TWIST1 mRNA expression with MFS, DFS or OS was observed in ER-negative patients. Genes highly correlated with TWIST1 were significantly enriched for cell adhesion and ECM-related signaling pathways. Furthermore, TWIST1 mRNA was highly expressed in tumor stroma and positively related to tumor stromal content (P <0.001). TWIST1 mRNA expression is an independent prognostic factor for poor prognosis in LNN/ER-positive breast cancer. The biological associations suggest an involvement of the tumor microenvironment in TWIST1's adverse role in breast cancer.
登录
查看更多内容
影响因子：
10.4
作者：
Tong W;Cao X;Harris S;Sun H;Fang H;Fuscoe J;Harris A;Hong H;Xie Q;Perkins R;Shi L;Casciano D
通讯作者：
Casciano D
DOI：
10.1016/j.urolonc.2007.12.012
发表时间：
2009-05-01
影响因子：
2.7
作者：
Fondrevelle, Marie E.;Kantelip, Bernadette;Wallerand, Herve
通讯作者：
Wallerand, Herve
影响因子：
3.8
作者：
Soini Y;Tuhkanen H;Sironen R;Virtanen I;Kataja V;Auvinen P;Mannermaa A;Kosma VM
通讯作者：
Kosma VM
影响因子：
11.2
作者：
Smid, Marcel;Wang, Yixin;Martens, John W. M.
通讯作者：
Martens, John W. M.
影响因子：
11.5
作者：
Sieuwerts, AM;Look, MP;Foekens, JA
通讯作者：
Foekens, JA