GPI-80 as a Useful Index for Myeloid Cell Heterogeneity and a Potential Prognostic Biomarker for Metastatic Renal Cell Carcinoma
GPI-80 as a Useful Index for Myeloid Cell Heterogeneity and a Potential Prognostic Biomarker for Metastatic Renal Cell Carcinoma
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DOI：
10.1620/tjem.249.203
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发表时间：
2019-11-01
影响因子：
2.2
通讯作者：
Tsuchiya, Norihiko
中科院分区：
文献类型：
--
作者：
Kato, Tomoyuki;Takeda, Yuji;Tsuchiya, Norihiko
骨髓来源的抑制细胞（MDSC），包括嗜中性MDSC和单核细胞MDSC，表现出高免疫抑制活性。糖基磷脂酰肌醇锚定的80 kD蛋白（GPI-80）选择性地表达在健康个体的成熟中性粒细胞上。单核细胞上GPI-80表达的增加和中性粒细胞上GPI-80表达的变化表明癌症患者外周血中MDSC的出现。然而，目前尚不清楚骨髓细胞、嗜中性MDSC和单核细胞MDSC上的GPI-80表达是否与癌症患者的临床结果相关。在这项研究中，我们研究了表达GPI-80的髓样细胞的特征以及GPI-80表达在转移性肾细胞癌（mRCC）患者临床结局中的意义，其中原发性肾细胞癌从肾脏扩散到其他器官。该研究包括20名mRCC患者（平均年龄66.0岁）和16名健康志愿者（平均年龄47.8岁）。为了确定外周血样本中髓样细胞的异质性，我们使用GPI-80、CD 16和潜伏相关肽-1（LTP）（来源于转化生长因子β 1前体的N-末端区域）的组合进行了三维主成分分析。结果显示，mRCC患者的髓系细胞分布广泛，与健康志愿者的髓系细胞有明显区别。生存分析显示中性粒细胞和单核细胞上GPI-80的表达与mRCC患者的不良预后结果相关。总之，髓系细胞上GPI-80的表达是MDSC异质性的有用指标，可作为mRCC的潜在预后生物标志物。
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-beta 1 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.