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Prognostic Significance of CDCP1 Expression in Colorectal Cancer and Effect of Its Inhibition on Invasion and Migration

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

This work was supported by Grants from National Science Council, Taiwan (NSC 99-2314-B-002-083-MY3), National Taiwan University Hospital (NTUH.100-S1508), and Chang Gung Medical Research Foundation, Taiwan (CMRPF6A0043, CMRPF6C0061 and CMRPF6C0062). We thank Dr. Zee-Fen Chang (Institute of Biochemistry and Molecular Biology, College of Medicine and National Yang-Ming University, Taipei, Taiwan, R.O.C.) for providing the ROCK1 plasmid and antibody.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi, Taiwan

    Chiang-Ting Chou PhD

  2. Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, Taiwan

    Chiang-Ting Chou PhD

  3. Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

    Yue-Ju Li PhD & Cheng-Chi Chang PhD

  4. Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan

    Cheng-Chi Chang PhD, Cheng-Ning Yang PhD & Pei-Shan Li

  5. Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan

    Cheng-Chi Chang PhD & Been-Ren Lin PhD

  6. Department of Otolaryngology National Taiwan University Hospital College of Medicine, National Taiwan University, Taipei, Taiwan

    Cheng-Ning Yang PhD

  7. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

    Pei-Shan Li & Been-Ren Lin PhD

  8. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

    Yung-Ming Jeng PhD

  9. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

    Szu-Ta Chen PhD

  10. College of Science, National Taiwan University, Taipei, Taiwan

    Min-Liang Kuo PhD

  11. Department of Family Medicine, Changhua Christian Hospital, Taipei, Taiwan

    I-Ching Lin MD

  12. Faculty of Medicine, Chung Shan Medical University, Taipei, Taiwan

    I-Ching Lin MD

  13. Faculty of Medicine, Kaohsiung Medical University, Taipei, Taiwan

    I-Ching Lin MD

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  1. Chiang-Ting Chou PhD
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  2. Yue-Ju Li PhD
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Correspondence to Been-Ren Lin PhD.

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Equal contribution

Yue-Ju Li and Cheng-Chi Chang contributed equally to this article

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Chou, CT., Li, YJ., Chang, CC. et al. Prognostic Significance of CDCP1 Expression in Colorectal Cancer and Effect of Its Inhibition on Invasion and Migration. Ann Surg Oncol 22, 4335–4343 (2015). https://doi.org/10.1245/s10434-015-4505-4

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  • DOI: https://doi.org/10.1245/s10434-015-4505-4

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