Abstract 1084: Clinical significance of p63/miR-138 deregulation in tongue squamous cell carcinoma

Abstract

Abstract BACKGROUND and AIMS: p63 is critical for the development and maintenance of stratified epithelial tissues. The role of p63 in tumorigenesis remains poorly defined. This study aims to determine the levels of p63 and miR-138 expression both in vitro and in vivo, and further to analyze their correlation with the clinicopathological parameters and prognosis in patients with tongue squamous cell carcinoma (TSCC). METHODS: Levels of p63 and miR-138 in TSCC and paired para-cancerous tissues were investigated by immunohistochemistry (IHC) and in situ hybridization (ISH), respectively. The correlations of p63 and miR-138 expression with the clinico- pathological parameters and prognosis of patients with TSCC were analyzed using SPSS 13.0 software package. Expression of p63 and miR-138 in TSCC cell lines (n = 5) was measured using immunoblot analysis and qRT-PCR, respectively. p63 was expressed transgenically, or knocked down with shRNAs in SCC9, SCC25, SCC15 and UM1 cell lines, and effects on cell invasion and migration were evaluated. RESULTS: Elevated level of p63 and reduced level of miR-138 was observed in TSCC tissues in comparison with paired para-cancerous tissues (p < 0.05). In particular, a more elevated expression for p63 appeared in the invasive tumor front compared with superficial or central parts of the primary tissues (p < 0.05). A negative correlation between p63 and miR-138 expression can be observed in the TSCC tissues. Statistical analysis revealed that p63 and miR-138 expression level are associated with cell differentiation, cervical lymph node metastasis status and clinical stage as well in patients with TSCC. COX regression analysis shows that p63 over-expression was correlated with reduced overall survival. P63 can be served as an independent prognostic factor for patients with TSCC. These observations were confirmed in vitro, in which ΔNp63 is the predominant p63 isoform expressed in the TSCC cell lines, and a negative correlation between p63 and miR-138 expression can be observed (p < 0.05). Ectopic transfection of p63 led to reduce miR-138 expression and enhanced cell invasion and migration. On the contrary, knockdown of p63 enhanced miR-138 expression and suppressed cell invasion and migration. Furthermore, transfection of miR-138 partly reversed cell invasion and migration induced by p63 overexpression. CONCLUSION: The dysregulation of p63 and miR-138 are common molecular events in TSCC progression. These findings suggest that p63 and miR-138 may collaboratively play a role in tongue carcinogenesis. Citation Format: Zehang Zhuang, Yun Wang, Cheng Wang, Nan Xie, Yue Wu, Jinsong Hou, Xiqiang Liu, Hongzhang Huang. Clinical significance of p63/miR-138 deregulation in tongue squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1084.