Chou Chiang-Ting, Li Yue-Ju, Chang Cheng-Chi, Yang Cheng-Ning, Li Pei-Shan, Jeng Yung-Ming, Chen Szu-Ta, Kuo Min-Liang, Lin I-Ching, Lin Been-Ren
Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi, Taiwan.
Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, Taiwan.
Ann Surg Oncol. 2015 Dec;22(13):4335-43. doi: 10.1245/s10434-015-4505-4. Epub 2015 Mar 28.
To assess the correlations and functions of complement C1r/C1s, Uegf, Bmp1 domain-containing protein-1 (CDCP1) in identifying colorectal cancer (CRC) patients who are at high risk for metastasis.
Tumor specimens from 101 patients were analyzed by real-time polymerase chain reaction to detect CDCP1 expression. CDCP1 expression plasmids and shRNA were used to knock down CDCP1 expression in this study to investigate migratory and invasive abilities by Boyden chambers. The mRNA expression profiles in shCDCP1 transfectants were compared to those in control cells by conducting microarray analysis. Its downstream effectors were also invested in this study.
CRC patients with a high CDCP1 expression had a statistically significant lower overall survival and disease-free survival compared to those exhibiting low CDCP1 expression. In vitro, knock-down CDCP1 expression significantly decreased migratory and invasive abilities in HCT116. Aberrant expression of CDCP1 increased cancer cell migration and invasion. By using integrated genomics, we identified ROCK1 (rho-associated, coiled-coil-containing protein kinase 1 pseudogene 1) as a downstream effector in CDCP1-mediated migration and as an invasion mediator. Clinically, ROCK1 and CDCP1 mRNA expression exhibited a strong positive correlation in CRC patient samples.
Our results implicated CDCP1 as a key regulator of CRC migration and invasion, and suggest that it is a useful prognostic factor for patients with CRC. Improved identification of a high-risk subset of early metastatic patients may guide indications of individualized treatment in clinical practice.
评估补体C1r/C1s、Uegf、含Bmp1结构域蛋白1（CDCP1）在识别具有高转移风险的结直肠癌（CRC）患者中的相关性及作用。
采用实时聚合酶链反应分析101例患者的肿瘤标本，以检测CDCP1表达。本研究使用CDCP1表达质粒和短发夹RNA（shRNA）敲低CDCP1表达，通过Boyden小室法研究其迁移和侵袭能力。通过微阵列分析比较shCDCP1转染细胞与对照细胞的mRNA表达谱。本研究还探究了其下游效应分子。
与低CDCP1表达的CRC患者相比，高CDCP1表达的患者总生存期和无病生存期在统计学上显著更低。在体外，敲低HCT116细胞中的CDCP1表达可显著降低其迁移和侵袭能力。CDCP1的异常表达增加了癌细胞的迁移和侵袭。通过综合基因组学，我们鉴定出ROCK1（rho相关的含卷曲螺旋蛋白激酶1假基因1）是CDCP1介导的迁移中的下游效应分子及侵袭介导因子。临床上，在CRC患者样本中，ROCK1和CDCP1 mRNA表达呈强正相关。
我们的结果表明CDCP1是CRC迁移和侵袭的关键调节因子，并提示它是CRC患者有用的预后因素。更好地识别早期转移患者的高危亚组可能会指导临床实践中的个体化治疗指征。
