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Clinical Significance of Signal Regulatory Protein Alpha (SIRPα) Expression in Hepatocellular Carcinoma

  • Hepatobiliary Tumors
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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Signal regulatory protein alpha (SIRPα), expressed in the macrophage membrane, inhibits phagocytosis of tumor cells via CD47/SIRPα interaction, which acts as an immune checkpoint factor in cancers. This study aimed to clarify the clinical significance of SIRPα expression in hepatocellular carcinoma (HCC).

Methods

This study analyzed SIRPα expression using RNA sequencing data of 372 HCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical staining of our 189 HCC patient cohort. The correlation between SIRPα expression and clinicopathologic factors, patient survival, and intratumor infiltration of immune cells was investigated.

Results

Overall survival (OS) was significantly poorer with high SIRPα expression than with low expression in both TCGA and our cohort. High SIRPα expression correlated with lower recurrence-free survival (RFS) in our cohort. High SIRPα expression was associated with higher rates of microvascular invasion and lower serum albumin levels and correlated with greater intratumor infiltration of CD68-positive macrophages and myeloid-derived suppressor cells (MDSCs). Multivariate analysis showed that SIRPα expression and high infiltration of CD8-positive T cells and MDSCs were predictive factors for both RFS and OS. Patients with high SIRPα expression and infiltration of CD8-positive T cells and MDSCs had significantly lower RFS and OS rates. In spatial transcriptomics sequencing, SIRPα expression was significantly correlated with CD163 expression.

Conclusions

High SIRPα expression in HCC indicates poor prognosis, possibly by inhibiting macrophage phagocytosis of tumor cells, promoting MDSC infiltration and inducing antitumor immunity. Treatment alternatives using SIRPα blockage should be considered in HCC as inhibiting macrophage antitumor immunity and MDSCs.

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Acknowledgment

This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant No. JP-19K09198) and the Research Grant of the Princess Takamatsu Cancer Research Fund.

Author information

Authors and Affiliations

  1. Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Takahiro Tomiyama MD, PhD, Shinji Itoh MD, PhD, Norifumi Iseda MD, PhD, Katsuya Toshida MD, Yukiko Kosai-Fujimoto MD, PhD, Takahiro Tomino MD, PhD, Takeshi Kurihara MD, PhD, Yoshihiro Nagao MD, PhD, Kazutoyo Morita MD, PhD, Noboru Harada MD, PhD & Tomoharu Yoshizumi MD, PhD

  2. Single-Cell Genomics, Human Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan

    Yu-Chen Liu PhD & Daisuke Ozaki PhD

  3. Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

    Daisuke Ozaki PhD

  4. Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan

    Daisuke Ozaki PhD

  5. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Kenichi Kohashi MD, PhD & Yoshinao Oda MD, PhD

  6. School of Medicine, Tokai University, Kanagawa, Japan

    Masaki Mori MD, PhD

Authors
  1. Takahiro Tomiyama MD, PhD
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  2. Shinji Itoh MD, PhD
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  16. Tomoharu Yoshizumi MD, PhD
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Corresponding author

Correspondence to Shinji Itoh MD, PhD.

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Tomiyama, T., Itoh, S., Iseda, N. et al. Clinical Significance of Signal Regulatory Protein Alpha (SIRPα) Expression in Hepatocellular Carcinoma. Ann Surg Oncol 30, 3378–3389 (2023). https://doi.org/10.1245/s10434-022-13058-y

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  • DOI: https://doi.org/10.1245/s10434-022-13058-y

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