Abstract

Abstract Background Hepatic metastasis and relapse contribute to the high incidence of gastric cancer (GC)-related fatalities, and represent a frequent and crucial problem for oncologists. Knowledge of the unique molecular attributes to hepatic metastasis will improve our understanding of the biology of metastatic GC and facilitate development of specific biomarkers and appropriate targeted therapies, leading to efficacious personalized treatment. Methods Transcriptome and bioinformatics analyses were conduct to identify a candidate molecule that specifically mediate hepatic recurrences of GC. Small interfering RNA (siRNA) experiments to determine the effect of knockdown on phenotype. Expression levels of the candidate molecule was determined in the gastric tissues of 200 patients with GC. Results Asialoglycoprotein receptor 2 (ASGR2), a membrane trafficking protein, was identified as a candidate biomarker specific to hepatic metastasis. Transcription levels of ASGR2 were differential among GC cell lines and increased compared to a control nontumorigenic epithelial cell line. Inhibiting ASGR2 expression decreased the invasion and migration abilities of GC cells. Increased expression of ASGR2 mRNA in GC tissues was significantly associated with lymphatic involvement, vessel invasion, advanced stage and hepatic metastasis. In patient subgroup of stage II GC, those with increased ASGR2 expression had significantly shorter overall and disease-free survival than those without. Conclusions ASGR2 may represent a biomarker for hepatic metastasis of GC and as a target for therapy. Citation Format: Haruyoshi Tanaka. Roles of asialoglycoprotein receptor 2 in gastric cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3112. doi:10.1158/1538-7445.AM2017-3112

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