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Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer

  • Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The NKG2A/HLA-E pathway functions as an immune checkpoint with potential for inhibition using therapeutic antibodies. Through this pathway, immune cells lose activity, which allows cancers to progress. We aimed to determine whether HLA-E expression combined with NK cell status serves as a prognostic biomarker for gastric cancer (GC).

Methods

We enrolled patients (n = 232) with advanced GC who underwent curative gastrectomy. Immunohistochemical analyses of global HLA-E expression, and the expression of CD56 and CD3 to identify NK cells were performed. Survival analysis was performed to evaluate the significance of HLA-E expression and NK status.

Results

Patients with HLA-E-positive was 104 (41.3%) and had significantly worse prognosis of relapse-free survival (RFS) compared with those with HLA-E-negative. Moreover, patients with NK Low status had worse prognoses for RFS compared with those with NK High status. Statistical analysis of RFS demonstrated that HLA-E expression was a significant independent factor for poor prognosis (HR 1.57, 95% CI 1.04–2.36, P = 0.031). Furthermore, HLA-E-positive patients with low NK low status experienced the shortest RFS, particularly those in the upper GC group.

Conclusions

HLA-E served as a prognostic factor after curative resection of GC, and HLA-E expression combined with NK status served as a sensitive prognostic biomarker for advanced GC.

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Acknowledgment

The authors thank Edanz Group (https://en-author-services.edanz.com/ac) for editing a draft of this manuscript. All authors had no source of funding related to this work.

Funding

This work was supported in part by the following grant and foundation: Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research; grant number 20K07594 and 20K16308.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Takeshi Morinaga MD, Masaaki Iwatsuki MD, PhD, Kohei Yamashita MD, PhD, Chihiro Matsumoto MD, Kazuto Harada MD, PhD, Junji Kurashige MD, PhD, Shiro Iwagami MD, PhD, Yoshifumi Baba MD, PhD, Naoya Yoshida MD, PhD & Hideo Baba MD, PhD

  2. Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Yoshihiro Komohara MD, PhD

Authors
  1. Takeshi Morinaga MD
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  2. Masaaki Iwatsuki MD, PhD
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  3. Kohei Yamashita MD, PhD
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  4. Chihiro Matsumoto MD
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  5. Kazuto Harada MD, PhD
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  6. Junji Kurashige MD, PhD
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  7. Shiro Iwagami MD, PhD
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  8. Yoshifumi Baba MD, PhD
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  11. Hideo Baba MD, PhD
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Corresponding author

Correspondence to Masaaki Iwatsuki MD, PhD.

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The authors declare that they have no conflict of interest.

Ethical Approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its subsequent versions. Informed consent for inclusion in the study, or the equivalent, was obtained from all patients.

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Morinaga, T., Iwatsuki, M., Yamashita, K. et al. Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer. Ann Surg Oncol 29, 4951–4960 (2022). https://doi.org/10.1245/s10434-022-11665-3

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  • DOI: https://doi.org/10.1245/s10434-022-11665-3

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