Loss of CDCP1 expression promotes invasiveness and poor prognosis in esophageal squamous cell carcinoma.
BACKGROUND
Human CDCP1 gene, located on chromosome 3p21.3, is a transmembrane glycoprotein widely expressed in epithelial tissues, and its role in cancer remains to be understood.


METHODS
Using microarray profiles of gene expression and copy number data from 69 esophageal squamous cell carcinoma (ESCC) samples, we performed informatics analyses to reveal the significance of CDCP1 expression. We also performed migration and invasion assays of siRNA-targeted CDCP1-transfected cells and CDCP1-overexpressing cell in vitro. Moreover, we evaluated the clinical magnitude of CDCP1 expression in esophageal squamous cell cancer cases.


RESULTS
Allelic loss of chromosome 3p was confirmed by copy number analysis. The expression level of CDCP1 in tumor tissue was significantly lower than that in corresponding normal tissue. siRNA targeting of CDCP1 promoted the migratory and invasive abilities of esophageal cancer cell lines, whereas both abilities were reduced in CDCP1-overexpressing cells. Gene set enrichment analysis showed that expression levels of CDCP1 were associated with tumor differentiation and metastasis, consistent with the result of clinicopathologic analyses. Finally, multivariate analysis revealed that the expression level of CDCP1 was an independent prognostic factor for survival.


CONCLUSIONS
Loss of CDCP1 expression may be a novel indicator for biological aggressiveness in ESCC.
Department of Surgery, Beppu Hospital, Kyushu University, Beppu, Japan.
Genta
G
Sawada
Yusuke
Y
Takahashi
Atsushi
A
Niida
Teppei
T
Shimamura
Junji
J
Kurashige
Tae
T
Matsumura
Hiroki
H
Ueo
Ryutaro
R
Uchi
Yuki
Y
Takano
Masami
M
Ueda
Hidenari
H
Hirata
Shotaro
S
Sakimura
Yoshiaki
Y
Shinden
Hidetoshi
H
Eguchi
Tomoya
T
Sudo
Keishi
K
Sugimachi
Satoru
S
Miyano
Yuichiro
Y
Doki
Masaki
M
Mori
Koshi
K
Mimori
D000368:Aged; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D000951:Antigens, Neoplasm; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate; D014162:Transfection
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C432044:CDCP1 protein, human; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins