Abstract 1361: The clinicopathological significance of LSD1 in esophageal cancers

Abstract

Abstract Background: Lysine-specific demethylase 1 (LSD1) is the first discovered histone demethylase which specially removes H3K4me1/2 through a flavin-adenine-dinucleotide (FAD). Previous studies have indicated that LSD1 is associated with cell proliferation, cell invasion and epithelial-mesenchymal transition in human malignant tumors. Recently, it is accepted that LSD1 epigenetically regulates energy-expenditure genes in adipocytes depending on the cellular FAD availability. As a PET scan with a FDG tracer can detect cancers, the method is exceedingly useful for tumor staging or therapeutic effect determination of esophageal cancers. The aim of this study is to investigate the expression and function of LSD1 in esophageal cancer cell-lines and, to analyze the relationships between the LSD1 expression and clinicopathological data including SUVmax (standardized uptake value). Methods: The influence of LSD1 on cell proliferation and invasion was evaluated by knockdown experiments. Using 113 resected esophageal cancer specimens, we evaluated the LSD1 expression by immunohistochemistry and devided them into two groups; a low expression group (LEG) and a high expression group (HEG). We compared these two groups and analyzed the relationships between LSD1 expression and clinicopathological data. Results: In vitro analysis, knockdown of LSD1 did not impact cell proliferation, but suppressed cell invasion. In the immunohistochemical study, the HEG's age was significantly higher (P=0.021), and this group had esophageal cancers at lower locations (P=0.058). HEG was significantly correlated with the T-stage (P=0.020), lymph and blood vessels invasion (P=0.020, P=0.001), and a higher SUVmax (P=0.0088) and lower overall survival (P=0.0017). Conclusions: Our study demonstrated the relationships between the expression of LSD1 and T-stage, lymph and blood vessels invasion, and the SUVmax in esophageal cancers. It is suggested that LSD1 has a potential to impact the malignancy of the esophageal cancer, and may be a therapeutic target in patients with esophageal cancers. Citation Format: Keisuke Kosumi, Yoshifumi Baba, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Akihisa Sakamoto, Shinjiro Hino, Mitsuyoshi Nakao, Hideo Baba. The clinicopathological significance of LSD1 in esophageal cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1361. doi:10.1158/1538-7445.AM2014-1361