Mizuno Ryuichi, Kimura Go, Fukasawa Satoshi, Ueda Takeshi, Kondo Tsunenori, Hara Hidehiko, Shoji Sunao, Kanao Kent, Nakazawa Hayakazu, Tanabe Kazunari, Horie Shigeo, Oya Mototsugu
Department of Urology, School of Medicine, Keio University, Toyko, Japan.
Department of Urology, Nippon Medical School, Tokyo, Japan.
Cancer Sci. 2017 Sep;108(9):1858-1863. doi: 10.1111/cas.13320. Epub 2017 Aug 20.
The objective of this prospective study was to identify baseline angiogenic and inflammatory markers in serum as well as the baseline levels of immune cells in whole blood to predict progression-free survival in patients with metastatic renal cell carcinoma treated with sunitinib. Blood samples were collected at baseline in all 90 patients to analyze serum angiogenic and inflammatory markers together with peripheral blood immunological marker. The association between each marker and sunitinib efficacy was analyzed. Univariate and multivariate Cox proportional model analyses were used to assess the correlation between those markers with survival. Baseline levels of interleukin-6, interleukin-8, high sensitivity C-reactive protein and myeloid-derived suppressor cells were significantly higher in patients who progressed when compared with those with clinical benefit. Analysis by the Cox regression model showed that baseline interleukin-8, high sensitivity C-reactive protein and percentage of T helper type 1 cells were significantly associated with progression-free survival in univariate analysis. Furthermore, in multivariate analysis, those three markers were independent indices to predict progression-free survival. In conclusion, angiogenic (interleukin-8), inflammatory (interleukin-6, high sensitivity C-reactive) and immunologic (myeloid-derived suppressor cells, percentage of T helper type 1 cells) markers at baseline would predict the response to sunitinib therapy and/or disease progression in patients with metastatic renal cell carcinoma.
这项前瞻性研究的目的是确定血清中的基线血管生成和炎症标志物以及全血中免疫细胞的基线水平，以预测接受舒尼替尼治疗的转移性肾细胞癌患者的无进展生存期。在全部90例患者的基线期采集血样，以分析血清血管生成和炎症标志物以及外周血免疫标志物。分析了每种标志物与舒尼替尼疗效之间的关联。采用单因素和多因素Cox比例模型分析来评估这些标志物与生存率之间的相关性。与具有临床获益的患者相比，疾病进展的患者白细胞介素-6、白细胞介素-8、高敏C反应蛋白和髓源性抑制细胞的基线水平显著更高。Cox回归模型分析显示，在单因素分析中，基线白细胞介素-8、高敏C反应蛋白和1型辅助性T细胞百分比与无进展生存期显著相关。此外，在多因素分析中，这三种标志物是预测无进展生存期的独立指标。总之，基线时的血管生成（白细胞介素-8）、炎症（白细胞介素-6、高敏C反应蛋白）和免疫（髓源性抑制细胞、1型辅助性T细胞百分比）标志物可预测转移性肾细胞癌患者对舒尼替尼治疗的反应和/或疾病进展。
