Downregulation of carcinoembryonic antigen-related cell adhesion molecule 1 in oral squamous cell carcinoma: correlation with tumor progression and poor prognosis.
OBJECTIVE
To identify genes associated with therapeutic targets of oral squamous cell carcinoma (OSCC), we compared gene expression profiles in OSCC-derived cell lines with human normal oral keratinocytes.


METHODS
We analyzed the gene expression profiles of OSCCs using Affymetrix GeneChip analysis. The identified genes were analyzed by an Ingenuity Pathway Analysis tool to identify networks of interacting genes. A candidate gene was further evaluated for the expression status of the mRNA and protein in OSCC-derived cell lines and primary OSCCs.


RESULTS
The microarray data identified 188 genes downregulated in OSCC-derived cell lines, and the genetic pathways associated with expression changes were generated. Among the genes mapped to the network with the highest significance, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was analyzed further. CEACAM1 mRNA and protein were frequently downregulated in OSCC-derived cell lines compared with human normal oral keratinocytes. Immunohistochemical analysis showed that primary OSCCs were significantly decreased in CEACAM1. Moreover, CEACAM1 expression was correlated with the TNM staging. We also found that CEACAM1-negative expression was significant both for disease-free (p = 0.036) and overall survival (p = 0.032).


CONCLUSIONS
Repression of CEACAM1 could contribute to cancer progression and may indicate a poor prognosis for patients with OSCC.
Shinozuka
Keiji
K
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Uzawa
Katsuhiro
K
Fushimi
Kazuaki
K
Yamano
Yukio
Y
Shiiba
Masashi
M
Bukawa
Hiroki
H
Yokoe
Hidetaka
H
Tanzawa
Hideki
H
D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis
D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules