Identification of novel cancer-related gene, DTL in digestive tract cancer

虽然先前的研究已经确定了食道鳞状细胞癌(ESCC)中的各种扩增片段及其靶点，但最近人类基因组计划的进展促使我们确定了更多的靶点。在这项研究中，我们测试了位于先前报道的1q32-q41扩增子的DTL是否在ESCC中起促癌基因的作用。DTL蛋白在原发鳞状细胞癌中高表达，且与PN分期、复发状态显著相关。在多因素分析中，DTL高表达的肿瘤患者的总体生存率比不表达的肿瘤患者差，DTL是独立的预后因素。DTL基因的敲除抑制了ESCC细胞的生长，而异位过表达的DTL则促进了ESCC细胞的生长。这些发现表明DTL在肿瘤细胞生长中起着重要作用，并突出了它作为ESCC预后指标和潜在治疗靶点的作用。

Although previous studies have identified various amplifications and their targets in esophageal squamous cell carcinoma (ESCC), recent progress in the human genome project prompted us to identify additional targets. In this study, we tested whether DTL, located at previously reported 1q32-q41 amplicon, acts as a cancer-promoting gene in ESCC. Overexpression of DTL protein was frequently detected in primary ESCCs, and significantly correlated with pN category, and status of recurrence. Patients with DTL-overexpressing tumors had a worse overall survival than those with non-expressing tumors, and DTL was independent prognosticator in the multivariate analysis. Knockdown of DTL inhibited and ectopic overexpression of DTL promoted the growth of ESCC cells. These findings suggest that DTL plays an important role in tumor cell growth, and highlight its usefulness as a prognosticator and potential therapeutic target in ESCC.