Prognostic Significance of CDCP1 Expression in Colorectal Cancer and Effect of Its Inhibition on Invasion and Migration
Journal
Annals of Surgical Oncology
Journal Volume
22
Journal Issue
13
Pages
4335-4343
Date Issued
2015
Author(s)
Chou C.-T.
Li Y.-J.
Chang C.-C.
Yang C.-N.
Li P.-S.
Chen S.-T.
Kuo M.-L.
Lin I.-C.
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. ? 2015, Society of Surgical Oncology.
SDGs
Other Subjects
complement component C1r; complement component C1s; domain containing protein 1; messenger RNA; procollagen C proteinase; protein; rho associated coiled coil-containing protein kinase 1 pseudogene 1; short hairpin RNA; uegf protein; unclassified drug; CDCP1 protein, human; cell adhesion molecule; leukocyte antigen; messenger RNA; small interfering RNA; tumor marker; tumor protein; adult; aged; animal experiment; animal model; Article; cancer prognosis; cancer staging; cell adhesion; cell migration; clinical practice; colorectal cancer; controlled study; correlation analysis; disease free survival; female; genomics; high risk patient; human; human cell; in vitro study; male; metastasis; microarray analysis; mouse; nonhuman; overall survival; plasmid; protein analysis; protein expression; protein function; real time polymerase chain reaction; recurrence free survival; tumor invasion; antagonists and inhibitors; cell motion; cell proliferation; colorectal tumor; follow up; genetics; lymph node metastasis; mortality; pathology; prognosis; reverse transcription polymerase chain reaction; survival rate; tumor cell culture; tumor recurrence; Aged; Antigens, CD; Biomarkers, Tumor; Cell Adhesion; Cell Adhesion Molecules; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Survival Rate; Tumor Cells, Cultured
Publisher
Springer New York LLC
Type
journal article