Identification of differentially expressed genes in oral squamous cell carcinoma

Abstract

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 a 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. ß 2004 Wiley-Liss, Inc.

Gene expression profile of oral squamous cell carcinomas from Sri Lankan betel quid users

“…There are several studies performed in OSCCs from western countries (14,32,(38)(39)(40), and some of the genes found in our study to be differentially expressed correlate with findings from western countries. These include in particular COL4A1, COL1A1, MMP1, PLAU, SPARC, TNC and KRT19, with MMP1 and PLAU as the most frequent genes.…”

Small Interfering RNA Targeting 14-3-3ζ Increases Efficacy of Chemotherapeutic Agents in Head and Neck Cancer Cells

“…We further showed that increased expression of these two 14-3-3 isoforms may serve as an adverse indicator for prognosis of head and neck cancers (11). Notably, we identified and verified increased expressions of 14-3-3ζ transcripts in oral squamous cell carcinoma in comparison with normal oral epithelium using differential display (12,13).…”

Cellular functions of 14-3-3ζ in apoptosis and cell adhesion emphasize its oncogenic character

“…In this analysis, 14-3-3z was clearly upregulated in human hepatocellular carcinoma, seminoma, pancreatic adenocarcinoma and several types of lung carcinoma (Figure 4). Similarly, studies on human stomach cancer (Jang et al, 2004), oral squamous-cell carcinoma (Arora et al, 2005) and breast cancer (Zang et al, 2004), have identified 14-3-3z among the most significantly increased proteins/genes in the tumours as compared to the corresponding normal tissues. Furthermore, 14-3-3z maps to human chromosome 8q23, a region frequently amplified in metastatic cancer (Tada et al, 2000;Ghadimi et al, 2003).…”