Abstract
Abstract This study aims to identify new biomarkers and therapeutic targets for oral cancer. Our strategies are as follows: i) Identification of overexpressed genes in oral cancers by gene expression array analysis, ii) Validation of clinicopathologic significance of their protein expression by tissue microarray, iii) Examination of their growth effect on cancer cell by siRNAs. We identified a secreted protein, OASEP1 (oral cancer-associated serum protein 1) as a candidate. Immunohistochemical staining showed that OASEP1 protein expression was observed in 120 (75.4%) of 159 oral cancers that had undergone curative surgery. High level of OASEP1 expression was associated with poor prognosis for oral cancer patients (P = 0.0054, by log-rank test). Multivariate analysis revealed that strong OASEP1 expression was an independent prognostic factor. Suppression of OASEP1 expression by siRNA specific for OASEP1 significantly inhibited the growth of oral cancer cell lines through apoptosis as detected by apoptosis assays and time lapse imaging. In addition, siRNAs for the receptor of OASEP1 also significantly inhibited the growth of oral cancer cells. Enforced OASEP1 expression significantly enhanced the growth of cancer cells. Addition of OASEP1 protein significantly increased the growth of oral cancer cells in a dose dependent manner, suggesting that the interaction between OASEP1 and its receptor regulated the growth of oral cancer cells. Microarray analysis coupled with siRNAs for OASEP1 demonstrated various OASEP1-related oncogenic pathways in oral cancer cells. Our data suggest that OASEP1 is a possible prognostic biomarker and therapeutic target for oral cancer. Citation Format: Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo. Characterization of OASEP1 as a biomarker and therapeutic target for oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5664.
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