Downregulation of carcinoembryonic antigen-related cell adhesion molecule 1 in oral squamous cell carcinoma: Correlation with tumor progression and poor prognosis

Keiji Shinozuka, Katsuhiro Uzawa, Kazuaki Fushimi, Yukio Yamano, Masashi Shiiba, Hiroki Bukawa, Hidetaka Yokoe, Hideki Tanzawa

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

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). Conclusion: Repression of CEACAM1 could contribute to cancer progression and may indicate a poor prognosis for patients with OSCC.

Original languageEnglish
Pages (from-to)387-397
Number of pages11
JournalOncology
Volume76
Issue number6
DOIs
Publication statusPublished - May 2009
Externally publishedYes

Keywords

  • Carcinoembryonic antigen-related cell adhesion molecule 1
  • Immunohistochemistry
  • Microarray analysis
  • Oral squamous cell carcinoma
  • Pathway analysis
  • Real-time quantitative reverse transcriptase-polymerase chain reaction
  • Western blot

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