Tohoku J. Exp. Med., 2019 November, 249(3)

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

TOMOYUKI KATO,¹ YUJI TAKEDA,² HIROMI ITO,¹ YUTA KUROTA,¹ ATSUSHI YAMAGISHI,¹ TOSHIHIKO SAKURAI,¹ SEI NAITO,¹ AKEMI ARAKI,² HIDETOSHI NARA,² HIRONOBU ASAO² and NORIHIKO TSUCHIYA¹

¹Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Yamagata, Japan
²Department of Immunology, Yamagata University Faculty of Medicine, Yamagata, Yamagata, Japan

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.

Keywords —— © 80 Tohoku University Medical Press

© 2019 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2019, 249, 203-212

Correspondence: Tomoyuki Kato, Department of Urology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, Yamagata 990-9585, Japan.

e-mail: kato-t@med.id.yamagata-u.ac.jp