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

虽然以前的研究已经确定了各种扩增及其在食管鳞状细胞癌（ESCC）的目标，在人类基因组计划的最新进展促使我们确定更多的目标。在这项研究中，我们测试是否DTL，位于先前报道的1 q32-q41扩增子，作为一个促癌基因在ESCC。DTL蛋白在原发性食管鳞癌中高表达，且与pN分级、复发状态显著相关。DTL过度表达肿瘤患者的总体生存率低于非表达肿瘤患者，DTL在多变量分析中是独立的决定因素。DTL的敲除抑制了食管鳞癌细胞的生长，而DTL的异位过表达促进了食管鳞癌细胞的生长。这些结果表明，DTL在肿瘤细胞生长中起着重要作用，并突出了其作为ESCC的促增殖剂和潜在治疗靶点的有用性。

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.