Mingsu Shi1, Yun Gu1, Kaifeng Jin1, Hanji Fang1, Yifan Chen2, Yifan Cao3, Xin Liu1, Kunpeng Lv1, Xudong He1, Chao Lin3, Hao Liu3, He Li3, Hongyong He3, Jing Qin3, Ruochen Li4, Heng Zhang5, Weijuan Zhang6. 1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. 2. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. 3. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. 4. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. rcli12@fudan.edu.cn. 5. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. zhang.heng@zs-hospital.sh.cn. 6. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. weijuanzhang@fudan.edu.cn.
Abstract
BACKGROUND: CD47 has been identified as an innate immune checkpoint and found to be associated with inferior survival in various types of cancer. However, the critical role of CD47 in gastric cancer and its association with tumor associated macrophages remain unclear. METHODS: Tumor tissues of gastric cancer from Zhongshan Hospital and data from GSE62254, GSE84437 and TCGA datasets were analyzed. Immunohistochemistry was performed to detect the expression of CD47, CD11c, CD163 and CD68 in gastric cancer tissues. Kaplan-Meier curves and Cox model were used for comparing the clinical outcomes of patients belonging to different subgroups. RESULTS: Gastric cancer patients with high CD47 expression exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT). A positive correlation was found between M1-polarized macrophage infiltration and CD47 expression in gastric cancer; however, the prognostic value of M1-polarized macrophages was attenuated in CD47-high gastric cancer patients. Moreover, we found that CD47 mRNA level was enriched in microsatellite-instable (MSI) subtype of gastric cancer and associated with ARID1A mutation and FGFR2 signaling pathway activation. CONCLUSIONS: Aberrant CD47 expression represented an independent predictor for adverse survival outcome and ACT resistance in gastric cancer. Targeting CD47 might be a promising strategy for gastric cancer patients.
BACKGROUND:CD47 has been identified as an innate immune checkpoint and found to be associated with inferior survival in various types of cancer. However, the critical role of CD47 in gastric cancer and its association with tumor associated macrophages remain unclear. METHODS:Tumor tissues of gastric cancer from Zhongshan Hospital and data from GSE62254, GSE84437 and TCGA datasets were analyzed. Immunohistochemistry was performed to detect the expression of CD47, CD11c, CD163 and CD68 in gastric cancer tissues. Kaplan-Meier curves and Cox model were used for comparing the clinical outcomes of patients belonging to different subgroups. RESULTS:Gastric cancerpatients with high CD47 expression exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT). A positive correlation was found between M1-polarized macrophage infiltration and CD47 expression in gastric cancer; however, the prognostic value of M1-polarized macrophages was attenuated in CD47-high gastric cancerpatients. Moreover, we found that CD47 mRNA level was enriched in microsatellite-instable (MSI) subtype of gastric cancer and associated with ARID1A mutation and FGFR2 signaling pathway activation. CONCLUSIONS: Aberrant CD47 expression represented an independent predictor for adverse survival outcome and ACT resistance in gastric cancer. Targeting CD47 might be a promising strategy for gastric cancerpatients.
Authors: Cristiana Tanase; Ana Maria Enciu; Elena Codrici; Ionela Daniela Popescu; Maria Dudau; Ana Maria Dobri; Sevinci Pop; Simona Mihai; Ancuța-Augustina Gheorghișan-Gălățeanu; Mihail Eugen Hinescu Journal: Int J Mol Sci Date: 2022-01-06 Impact factor: 5.923