Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Int J Oncol. 2010 Mar;36(3):563-8. doi: 10.3892/ijo_00000530.
Teratocarcinoma-derived growth factor 1 (TDGF1) is a member of the epidermal growth factor-cripto FRL1 cryptic protein family and is involved in the activation of several different signaling pathways during embryonic development and cellular transformation. Previous reports show that TDGF1 regulates the activation of several signaling pathways and controls cellular transformation in embryonic status, whereas its significance in colorectal cancer (CRC) is not yet fully understood. The present study comprised 55 patients who underwent surgery for CRC, as well as two cell lines derived from human CRC. The correlation of gene expression with clinical parameters in patients was assessed. The biological significance of TDGF1 expression was evaluated by knockdown experiments in the cell lines. Seventeen of 55 (30.9%) cases exhibited a higher TDGF1 expression in cancerous regions than in marginal non-cancerous regions. Patients with high TDGF1 expression were statistically susceptible to a recurrence of the disease, and showed poorer disease-free survival than those with low expression. The assessment of TDGF1 knock-down in the 2 cell lines demonstrated that the siRNA inhibition resulted in a statistically significant reduction in cell growth and invasion. In conclusion, the present data strongly suggest the usefulness of TDGF1 as a predictive marker for metachronous metastasis in CRC patients.
畸胎瘤衍生生长因子 1(TDGF1)是表皮生长因子-克里普托 FRL1 隐匿蛋白家族的成员,参与胚胎发育和细胞转化过程中几种不同信号通路的激活。先前的报告表明,TDGF1 调节几种信号通路的激活,并在胚胎状态下控制细胞转化,而其在结直肠癌(CRC)中的意义尚不完全清楚。本研究包括 55 例接受 CRC 手术的患者以及源自人 CRC 的两种细胞系。评估了基因表达与患者临床参数的相关性。通过细胞系中的敲低实验评估了 TDGF1 表达的生物学意义。在 55 例病例中,有 17 例(30.9%)癌症区域的 TDGF1 表达高于边缘非癌区域。TDGF1 高表达的患者在统计学上容易发生疾病复发,并且无病生存率低于低表达的患者。在 2 种细胞系中评估 TDGF1 敲低表明,siRNA 抑制导致细胞生长和侵袭的统计学显著降低。总之,本数据强烈表明 TDGF1 可作为 CRC 患者异时性转移的预测标志物。