Downregulation of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Oral Squamous Cell Carcinoma: Correlation with Tumor Progression and Poor Prognosis

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.

Upregulated expression of ADAM12 is associated with progression of oral squamous cell carcinoma

“…A tendency for decreased expression of ADAM33 mRNA in OSCC cell lines was also shown. These results were consistent with the data found in our previous DNA microarray analysis (13,16). Since mRNA expressions of other members of the ADAM family varied in OSCC cell lines examined, definitive conclusions could not be obtained.…”

“…We examined the mRNA expression levels of the six ADAM genes (ADAM9, ADAM10, ADAM12, ADAM17, ADAM28 and ADAM33) that showed significance in DNA microarray analysis performed previously (13,16). The present study revealed higher expression of ADAM12 mRNA in all OSCC cell lines examined when compared with HNOKs (Fig.…”

“…The intensity of the ADAM12 immunoreaction was scored as follows: 1+, weak; 2+, moderate; and 3+, intense. The percentage of positive tumor cells and the staining intensity then were multiplied to produce the immunohistochemical staining score (IHC score) (15,16). The maximum immunohistochemical staining score was 156.9 in normal tissues, therefore, cases in which the score was >156.9 were considered positive.…”

High prevalence of epigenetic inactivation of the human four and a half LIM domains 1 gene in human oral cancer

“…The results of microarray analysis provide researchers with high throughput screening to study the roles played by specific genes in cancer development and progression. We previously reported gene expression profiling of OSCC to identify cancer-related genes (5,6).…”

The roles of cell adhesion molecules in tumor suppression and cell migration

“…The characteristics and functions of CEACAM1 have been demonstrated in individual reports. CEACAM1 is frequently downregulated or dysregulated in multiple human tumors, [22][23][24][25] and is capable of suppressing cell growth and inducing apoptosis. [26][27][28] Ebrahimnejad et al demonstrated that exogenous expression of CEACAM1 enhances melanoma cell invasion and migration; and this enhanced motility can be reverted by anti-CEACAM antibodies.…”