Abstract 1547: LOXL1 is a novel responsible gene for peritoneal dissemination potentially via promoting EMT and motility in gastric cancer

Abstract

Abstract Background. In gastric cancer (GC), peritoneal dissemination (PD) occurs frequently and is incurable. We have identified 25 PD-associated genes in GC by in silico analysis in previous research. In this study, we focused on Lysyl oxidase-like 1 (LOXL1), one of the 25 PD-associated genes, because LOXL1 is a member of the lysyl oxidase (LOX) gene family and may have the ability to promote EMT in GC. Materials and Methods. We assessed LOXL1 expression using a public GC dataset (GSE15459) and a highly-disseminated peritoneal GC cell line (RT-qPCR). Next, we performed gene expression analysis, including gene set enrichment analysis (GSEA) with two public GC datasets (GSE15459 and TCGA). Moreover, we performed a series of in vitro experiments using GC cells. Finally, we evaluated the clinicopathological significance of LOXL1 expression using RT-qPCR and immunohistochemistry staining in the Kyushu cohort. We also performed survival analyses of LOXL1 expression in the Kyushu cohort, GSE15459, and TCGA datasets. Results. The expression of LOXL1 was higher in GC patients with PD compared with GC patients without PD in the GSE15459 dataset. LOXL1 was also overexpressed in highly-disseminated peritoneal GC cells relative to its control cells. Moreover, LOXL1 expression positively correlated with the EMT gene set in GSEA. Additionally, LOXL1 overexpression reduced CDH1 expression, increased VIM expression, CDH2 expression, SNAI2 expression, and PLS3 expression, and promoted migration capacity in GC cells. Finally, high LOXL1 expression was associated with poorly-differentiated, lymph node metastasis, and PD in the Kyushu cohort, and was a poor prognostic factor in three GC datasets. Conclusions. LOXL1 was a novel responsible gene for PD in GC, possibly through the activation of EMT and cell motility. Citation Format: Qingjiang Hu, Takaaki Masuda, Yoko Zaitsu, Yasuo Tsuda, Yuichi Hisamatsu, Yuichiro Nakashima, Koji Ando, Yasue Kimura, Eiji Oki, Masaki Mori, Koshi Mimori. LOXL1 is a novel responsible gene for peritoneal dissemination potentially via promoting EMT and motility in gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1547.