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CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration

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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.

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Data availability

All data generated that are relevant to the results presented in this article are included in this article. Other data that were not relevant for the results presented here are available from the corresponding author Dr. Zhang upon reasonable request.

Code availability

Not applicable.

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Acknowledgments

We thank Dr. Lingli Chen (Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China) and Dr. Peipei Zhang (Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) for their contribution to the evaluation of immunohistochemistry results and excellent pathological technology help.

Funding

This study was funded by grants from National Natural Science Foundation of China (81671628, 81871306, 81871926, 81871930, 81902402, 81902901, 81972219), Shanghai Municipal Natural Science Foundation (18ZR1432900), and Shanghai Sailing Program (17YF1402200, 18YF1404600, 19YF1407500). All these study sponsors have no roles in the study design, in the collection, analysis and interpretation of data.

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Author notes

  1. Mingsu Shi, Yun Gu, Kaifeng Jin and Hanji Fang contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Mingsu Shi, Yun Gu, Kaifeng Jin, Hanji Fang, Xin Liu, Kunpeng Lv & Xudong He

  2. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

    Yifan Chen & Weijuan Zhang

  3. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Yifan Cao, Chao Lin, Hao Liu, He Li, Hongyong He, Jing Qin, Ruochen Li & Heng Zhang

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  1. Mingsu Shi
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Contributions

M. Shi, Y. Gu, K. Jin and H. Fang for acquisition of data, analysis and interpretation of data, statistical analysis and drafting of the manuscript; Y. Chen, Y. Cao, X. Liu, K. Lv, X. He, C. Lin, H. Liu, H. Li, H. He and J. Qin for technical and material support; R. Li, H. Zhang and W. Zhang for study concept and design, analysis and interpretation of data, drafting of the manuscript, obtained funding and study supervision. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Ruochen Li, Heng Zhang or Weijuan Zhang.

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The protocol of all study was approved by the institutional review board and ethics committee of Zhongshan Hospital, Fudan University.

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Shi, M., Gu, Y., Jin, K. et al. CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration. Cancer Immunol Immunother 70, 1831–1840 (2021). https://doi.org/10.1007/s00262-020-02806-2

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