title: Prognostic Significance of CDCP1 Expression in Colorectal Cancer and Effect of Its Inhibition on Invasion and Migration.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.affiliation: Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yue-Ju
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.|Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan.
authors.forename: Cheng-Chi
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.|Department of Otolaryngology National Taiwan University Hospital College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Cheng-Ning
authors.initials: CN
authors.lastname: Yang
authors.affiliation: Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.|Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Li
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Szu-Ta
authors.initials: ST
authors.lastname: Chen
authors.affiliation: College of Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.affiliation: Department of Family Medicine, Changhua Christian Hospital, Taipei, Taiwan.|Faculty of Medicine, Chung Shan Medical University, Taipei, Taiwan.|Faculty of Medicine, Kaohsiung Medical University, Taipei, Taiwan.
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Lin
authors.affiliation: Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan. dtsurg92@yahoo.com.tw.|Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. dtsurg92@yahoo.com.tw.
authors.forename: Been-Ren
authors.initials: BR
authors.lastname: Lin
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000235:genetics*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000235:genetics*; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C432044:CDCP1 protein, human; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering