Validation of secreted protein OASEP1 as a prognostic biomarker and therapeutic target for oral cancer.

e18520 Background: Although current treatments for oral cancer (OC) include surgery, radiotherapy, and chemotherapy, their effectiveness is still limited. Therefore, the development of novel prognostic biomarkers and/or therapeutic agents is urgently needed. Methods: Our strategies are as follows: i) Identification of up-regulated genes in cancers by means of gene expression microarray, ii) Validation of clinicopathological significance of their protein expression by tissue microarray, iii) Examination of their growth effect on cancer cells by siRNAs and active ligand protein for growth assays. Results: We selected a secreted protein, OASEP1 (OC-associated serum protein 1) as a candidate. Real-Time qPCR and Western blotting showed that OASEP1 gene and its gene product were expressed in the majority of OC cells. Immunohistochemical staining showed that OASEP1 expression was observed in 73 (74.4%) of 98 OCs that had undergone curative surgery. In addition, high level of OASEP1 expression was associated with poor prognosis for OC patients ( P = 0.0158, by log-rank test). Suppression of OASEP1 expression by siRNAs for OASEP1 (si-OASEP1) significantly suppressed the growth and invasion of OC cell lines. Flowcytometry and live cell imaging showed that si-OASEP1 induced the apoptosis of OC cells. siRNAs against OASEP1-receptor also suppressed the growth of OC cells. Addition of active OASEP1 recombinant protein into culture media enhanced the growth of OC cells probably through AKT pathway. Our data suggest that OASEP1 and its receptor could play a significant role in the growth of OC cells in probable autocrine/paracrine manner. Conclusions: OASEP1 is a possible prognostic biomarker and therapeutic target for OC.