Expression of P8 in Oral Squamous Cell Carcinoma

Abstract

Oral cancer is a public health problem. Although the oral cavity is easily accessible as is the population at risk, early diagnosis has been painfully slow. As a result, the mortality rate from oral cancer for the past three and half decades remains high (over 50%) in spite of new treatment modalities. Early detection and treatment will increase the survival rates of oral cancer patients. Also the search for reliable predictors of oral cancer progression and prognosis remains a major challenge. The objective of the present study was to investigate the expression of p8, a transcription factor known to exhibit paradoxical expression and role in several human cancers, in archived tissues of human oral squamous cell carcinomas (OSCC) by immunohistochemistry in a retrospective study. Expression was thereafter correlated with clinical/outcome parameters. In addition, the effects of p8 silencing on some key tumorigenic hallmarks of oral carcinogenesis were investigated via lentiviral-mediated shRNA techniques. Results indicated that p8 is upregulated in ~85% of OSCCs. Although there was no correlation between p8 expression and clinical variables/prognostic outcome (except for the degree of tumor differentiation), p8 silencing resulted in decreased cell proliferation and a significant downregulation (>50%) of proliferation marker Ki-67 as well as the downregulation of two other gene products (CEBPβ and Nrf1). In conclusion, these results suggest that p8 may play a role in the pathways involving proliferation markers critical for oral cancer progression and metastatic spread. Moreover, the data provides a framework for future studies elaborating on p8 mechanistic networks involved in oral cancer biology. This is with a view to identifying target points for the design of potent vi biomimetics for intervention in oral cancer. Furthermore, the potential interaction of p8 with Nrf1 and CEBPβ presents another line of inquiry as to the mechanistic and/or functional implications and outcome of such biologic interaction.