Journal of Gastroenterology

, Volume 46, Issue 2, pp 153–163

DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness

  • Yuji Toiyama
  • Yasuhiro Inoue
  • Hiromi Yasuda
  • Susumu Saigusa
  • Takeshi Yokoe
  • Yoshinaga Okugawa
  • Koji Tanaka
  • Chikao Miki
  • Masato Kusunoki
Original Article—Alimentary Tract

DOI: 10.1007/s00535-010-0318-1

Cite this article as:
Toiyama, Y., Inoue, Y., Yasuda, H. et al. J Gastroenterol (2011) 46: 153. doi:10.1007/s00535-010-0318-1

Abstract

Background

We investigated changes in the gene expression profile in colon cancer in order to identify gene markers that may be useful in the management of this disease.

Methods

The Cancer Genome Anatomy Project was used to detect differences in gene expression between normal and cancer tissue. The overexpression of dipeptidase-1 (DPEP1) in cancer tissue was confirmed in a sample of 76 patients by real-time PCR. To identify the function of DPEP1, RNA interference (RNAi) was used to inactivate this gene in the colon cancer cell line. Immunohistochemical analysis was performed to characterize the pattern of DPEP1 expression in colon cancer.

Results

DPEP1 expression in cancer was significantly higher than that in normal tissue. However, DPEP1 expression decreased with pathological differentiation, lymph-node and distant metastasis. Patients with tumors with decreased DPEP1 expression showed a poorer prognosis, and this was also true of patients with tumors who are treated with curative intent. RNAi-mediated DPEP1 reduction in the colon cancer cell line did not result in cell proliferation or apoptosis, but was associated with an increased invasive ability. DPEP1 protein was observed on the apical side of the cancer cells, and is expressed in the early stages of carcinogenesis, even in adenomas of both sporadic colorectal cancer and familial adenomatous polyposis patients.

Conclusions

DPEP1 expression in normal colonic mucosa is very low, but it is highly expressed in colorectal adenoma and cancer specimens and is negatively correlated with parameters of pathological aggressiveness and poor prognosis. DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness.

Keywords

DPEP1Colorectal cancerPrognosisCancer invasionCarcinogenesis

Copyright information

© Springer 2010

Authors and Affiliations

  • Yuji Toiyama
    • 1
  • Yasuhiro Inoue
    • 1
  • Hiromi Yasuda
    • 1
  • Susumu Saigusa
    • 1
  • Takeshi Yokoe
    • 1
  • Yoshinaga Okugawa
    • 1
  • Koji Tanaka
    • 1
  • Chikao Miki
    • 1
  • Masato Kusunoki
    • 1
  1. 1.Department of Gastrointestinal and Pediatric SurgeryMie University Graduate School of MedicineTsuJapan