Abstract 1267: Identification and characterization of oncogenic methyltransferase ESOC1 as a diagnostic and therapeutic target for esophageal cancer
Authors: Daigo Yataro , Takano Atsushi , Nakamura Yusuke 
Published: July 2016

Abstract
Esophageal cancer is one of the most lethal malignancies of the digestive tract, and at the time of diagnosis most of the patients are at advanced stages. In spite of the use of current surgical techniques combined with various treatment modalities, such as radiotherapy and chemotherapy, the prognosis of esophageal cancer still remains poor. Therefore, further development of new anti-cancer drugs for this disease with minimum risk of adverse event is urgently awaited. To screen oncoantigens which could be used for the development of new diagnostic biomarkers as well as molecular targeted drugs and/or immunotherapy, we have established a screening system as follows; i) To identify overexpressed genes in esophageal cancers by genome-wide screening using the microarray representing 27,648 genes and pure populations of tumor cells taken from cancer tissues by laser microdissection, ii) To verify the candidate genes for their very low or absent expression in normal tissues by northern-blotting, iii) To validate the clinicopathological significance of their expression with tissue microarray covering hundreds of archived esophageal cancers, iv) To verify whether the target genes are essential for the growth or survival of cancer cells by RNAi and cell growth assays. During this process, we selected dozens of druggable oncoproteins with various enzymatic activities, and identified overexpression of metyltransferase ESOC1 (esophageal cancer-associated oncoprotein 1) in the majority of esophageal cancers and its scarce expression in normal tissues except testis. Immunohistochemical staining using tumor tissue microarrays consisting of 251 esophageal cancers demonstrated that ESOC1 expression was associated with poor prognosis (P = 0.0029 by log-rank test), and multivariate analysis confirmed its independent prognostic value (P = 0.0082). Suppression of ESOC1 expression with siRNA effectively suppressed the growth of cancer cells. ESOC1 has a SAM dependent methyltransferase domain, and we confirmed its methyltransferase activity for some small non-coding RNAs that were overexpressed in esophageal cancers. In addition, we confirmed that the exogenous expression of ESOC1 increased the growth activity of HEK293T cells, but the mutant ESOC1 did not have methyltransferase activity, and did not confer the growth promoting activity. Since ESOC1 plays a significant role in the cell growth and malignant nature of tumors, we suggest that ESOC1 is likely to be a prognostic biomarker and a potential therapeutic target for developing new anti-cancer drugs and cancer vaccines.
Citation Format: Yataro Daigo, Atsushi Takano, Yusuke Nakamura. Identification and characterization of oncogenic methyltransferase ESOC1 as a diagnostic and therapeutic target for esophageal cancer. [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 1267.