Rapid advances in multimodality
therapy have not significantly improved the overall 5-yr survival of
oral cancer patients in the past two decades, thereby underscoring the need for molecular
therapeutics. The development of new treatment strategies for more effective management of
oral cancer requires identification of novel
biological targets. Therefore, the aim of this study was to identify novel genes associated with oral
tumorigenesis by comparing gene expression profile of
oral squamous cell carcinomas (OSCCs) and matched nonmalignant oral epithelial tissues with differential display. Of the 180 differentially expressed cDNAs isolated, reamplified, and cloned into pGEMT-Easy Vector, 26 cDNAs were confirmed to be upregulated in OSCCs by reverse Northern blot analysis. The differentially expressed genes included components of immune system, signaling pathways, angiogenesis, cell structure, proliferation, apoptosis, cell-adhesion, and cellular metabolism. Reverse transcription (RT)-polymerase chain reaction (PCR) analysis of 15 OSCCs and matched nonmalignant oral tissues provided the first evidence that 14-3-3-zeta,
melanoma metastasizing clone D (MEMD), KIAA0471, sperm
protein 17 (SP17), TC21, and anti-
TNF alpha antibody are upregulated in OSCCs. Immunohistochemical analysis confirmed overexpression of 14-3-3-zeta and TC21
protein, a member of the Ras family, in OSCCs as compared to histologically normal oral tissues validating the differential display analysis. Identification of six novel differentially expressed genes in oral
tumors adds to the repertoire of genes associated with oral
carcinogenesis and provides candidate potential
biological targets for diagnosis and/or
therapy. Further characterization of the 14 unknown differentially expressed cDNAs identified in this study may provide significant clues for understanding the molecular mechanisms underlying oral
tumorigenesis.