Affiliation:
1. Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital & Institute Beijing China
2. Department of Gastroenterology, Aerospace Center Hospital Peking University Aerospace School of Clinical Medicine Beijing China
3. Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital and Institute Beijing China
Abstract
Death receptor 5 (DR5) can inhibit malignant proliferation via tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptosis in many cancers. Here we examined the expression and sublocalization of DR5 in gastric cancer, as well as its effects on clinical prognosis and cellular processes. Our analysis included a cohort of 240 gastric cancer patients. Bioinformatic analysis showed a significant correlation between DR5 and DNA replication, tumor mutation burden (TMB), and tumor stemness. Unlike death receptor 4 (DR4TRAIL‐R1), DR5 was expressed in the cytoplasm and nucleus, and was found to be positively correlated with lymphovascular invasion, lymph node metastasis, and TNM stage. Patients with positive DR5 had worse overall survival (OS) (P = 0.006). The multivariate Cox model showed that DR5 is an independent poor prognostic factor (hazard ratio = 1.693). Furthermore, knockdown of DR5 inhibited aggressive behaviors, including proliferation and metastasis in gastric cancer cells, and inhibited lung metastasis in vivo. In summary, nuclear localization of DR5 expression is a poor prognosis factor in gastric cancer and promotes growth, invasion, and metastasis of tumor cells in vitro and in vivo.
Funder
Beijing Municipal Administration of Hospitals
National Natural Science Foundation of China
Beijing Municipal Natural Science Foundation
Subject
General Biochemistry, Genetics and Molecular Biology
Cited by
1 articles.
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