DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness.
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.
Toiyama
Yuji
Y
Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Inoue
Yasuhiro
Y
Yasuda
Hiromi
H
Saigusa
Susumu
S
Yokoe
Takeshi
T
Okugawa
Yoshinaga
Y
Tanaka
Koji
K
Miki
Chikao
C
Kusunoki
Masato
M
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018938:Caco-2 Cells; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004150:Dipeptidases / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D012333:RNA, Messenger; D004150:Dipeptidases; C549872:dipeptidase 1
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