Abstract 3555: TREM2 is upregulated and plays oncogenic role in gastric cancer

Background Triggering receptor expressed on myeloid cells-2 (TREM2) is thought to be invovled in innate immunity and inflammation regulation. More recently, the importance of TREM2 has been highlighted by identification in several kinds of solid tumors. Nonetheless, the oncogenic roles and potential molecular mechanisms of TREM2 in gastric cancer (GC) remain unknown. Methods The expression levels of TREM2 were determined by quantitative PCR (qPCR) and immunohistochemistry (IHC). MTT, colony formation, 5-Ethynyl-2′-deoxyuridine (EdU) incorporation, and in vivo tumorigenicity assays were performed to determine the pro-proliferative role of TREM2 in GC cells. mRNA sequencing, qPCR, and Western blotting were used to explore the underlying molecular mechanism of pro-proliferative role of TREM2 in GC cells. Results The mRNA expression of TREM2 was markedly up-regulated in tumor tissues (n=16) in comparison with that in corresponding non-tumorous tissues. Immunohistochemical study were performed to determine the protein expression in 108 patients with surgically resected GC. Its expression was positively associated with TNM stage (P=0.023) and T classification (P=0.021), and was inversly correlated with the poor clinical outcome of the patients. The human GC cell lines MGC-803 and BGC-823 were used for proliferation analysis. The transfected GC cell lines with stable overexpression of TREM2 were established. Ectopic overexpression of TREM2 in GC cells promoted cell proliferation, whereas loss of TREM2 function inhibited proliferation. In vivo animal experiments further validated the pro-proliferative role of TREM2. Deep sequencing to profile global gene expression of MGC-803 cells with TREM2 overexpression. In the biological process analysis, these differentially expressed genes were mainly involved in the MAPK signaling. Molecular mechanistic investigations explored that TREM2 upregulated GREM1 expression, thereby activating ERK1/2 signaling via VEGFR2-PLC-γ-PKC axis and promoting GC cell proliferation. Conclusion High TREM2 expression predicts poor prognosis in GC and TREM2 promotes GC cells proliferation. Our findings suggest that GREM1-VEGFR2-PLC-γ-PKC-ERK1/2 signaling axis contributes to the oncogenic roles of TREM2 on GC cells. TREM2 could be an effective prognostic biomarker and a potential therapeutic target. Citation Format: Yulong Zheng, Lihua Jiang, Cheng Xiao, Nong Xu, Qiqi Gao, Yinan Yao, Yongxian Hu, Yun Sun, Xin Xu. TREM2 is upregulated and plays oncogenic role in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3555.