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Identification of differentially expressed genes in oral squamous cell carcinoma
Shilpi Arora1, Ajay Matta, Nootan Kumar Shukla
1Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
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 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.
Insights
This study identified six novel genes, including 14-3-3-zeta and TC21, upregulated in oral squamous cell carcinomas (OSCCs). These findings offer potential new molecular targets for oral cancer diagnosis and therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multimodality therapy has not significantly improved 5-year survival for oral cancer patients.
- Novel molecular targets are crucial for developing more effective oral cancer treatments.
- Understanding oral tumorigenesis requires identifying genes involved in cancer development.
Purpose of the Study:
- To identify novel genes associated with oral squamous cell carcinoma (OSCC) tumorigenesis.
- To compare gene expression profiles between OSCC tissues and matched nonmalignant oral tissues.
- To discover potential new biological targets for oral cancer diagnosis and therapy.
Main Methods:
- Differential display technique was used to compare gene expression between OSCC and normal oral tissues.
- Upregulated cDNAs were confirmed using reverse Northern blot and Reverse Transcription-Polymerase Chain Reaction (RT-PCR).
- Immunohistochemistry was employed to validate protein overexpression of selected genes (14-3-3-zeta and TC21).
Main Results:
- 180 differentially expressed cDNAs were identified, with 26 confirmed as upregulated in OSCCs.
- Six specific genes, including 14-3-3-zeta, melanoma metastasizing clone D (MEMD), KIAA0471, sperm protein 17 (SP17), TC21, and anti-TNF alpha antibody, were found to be upregulated.
- Overexpression of 14-3-3-zeta and TC21 proteins was confirmed in OSCC tissues.
Conclusions:
- The study identified six novel differentially expressed genes in oral tumors, contributing to the understanding of oral carcinogenesis.
- These identified genes, such as 14-3-3-zeta and TC21, represent potential biological targets for oral cancer diagnosis and/or therapy.
- Further investigation into the 14 unknown differentially expressed cDNAs may elucidate molecular mechanisms underlying oral tumorigenesis.
