GPI-80 as a Useful Index for Myeloid Cell Heterogeneity and a Potential Prognostic Biomarker for Metastatic Renal Cell Carcinoma

  • Kato Tomoyuki
    Department of Urology, Yamagata University Faculty of Medicine
  • Takeda Yuji
    Department of Immunology, Yamagata University Faculty of Medicine
  • Ito Hiromi
    Department of Urology, Yamagata University Faculty of Medicine
  • Kurota Yuta
    Department of Urology, Yamagata University Faculty of Medicine
  • Yamagishi Atsushi
    Department of Urology, Yamagata University Faculty of Medicine
  • Sakurai Toshihiko
    Department of Urology, Yamagata University Faculty of Medicine
  • Naito Sei
    Department of Urology, Yamagata University Faculty of Medicine
  • Araki Akemi
    Department of Immunology, Yamagata University Faculty of Medicine
  • Nara Hidetoshi
    Department of Immunology, Yamagata University Faculty of Medicine
  • Asao Hironobu
    Department of Immunology, Yamagata University Faculty of Medicine
  • Tsuchiya Norihiko
    Department of Urology, Yamagata University Faculty of Medicine

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Abstract

<p>Myeloid-derived suppressor cells (MDSCs), which include neutrophilic MDSCs and monocytic MDSCs, exhibit high immunosuppressive activity. Glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80) is selectively expressed on mature neutrophils in healthy individuals. Increased GPI-80 expression on monocytes and variations in GPI-80 expression on neutrophils indicate the appearance of MDSCs in the peripheral blood of cancer patients. However, it is still unclear whether GPI-80 expression on myeloid cells, neutrophilic MDSCs and monocytic MDSCs, is correlated with the clinical outcomes of patients with cancer. In this study, we investigated the characteristics of myeloid cells expressing GPI-80 and the implication of GPI-80 expression in the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC), in which primary renal cell carcinoma spreads from the kidney to other organs. The study included 20 patients with mRCC (a mean age of 66.0 years) and 16 healthy volunteers (a mean age of 47.8 years). To determine the heterogeneity of myeloid cells in peripheral blood samples, we performed the three-dimensional principal component analysis using the combination of GPI-80, CD16, and latency-associated peptide-1 (LAP), derived from the N-terminal region of transforming growth factor-β1 precursor. The results showed that myeloid cells in mRCC patients were widely distributed and clearly distinguishable from those in the healthy volunteers. The survival analysis revealed that GPI-80 expression on neutrophils and monocytes was correlated with poor prognostic outcomes of patients with mRCC. In conclusion, the expression of GPI-80 on myeloid cells, a useful index for the heterogeneity of MDSCs, serves as a potential prognostic biomarker for mRCC.</p>

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