Neutrophil count is associated with myeloid derived suppressor cell level and presents prognostic value of for hepatocellular carcinoma patients.
Neutrophil count is associated with myeloid derived suppressor cell level and presents prognostic value of for hepatocellular carcinoma patients.
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中性粒细胞计数与骨髓源性抑制细胞水平相关，对肝细胞癌患者具有预后价值
DOI：
10.18632/oncotarget.15456
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发表时间：
2017-04-11
期刊：
影响因子：
--
通讯作者：
Zhou J
中科院分区：
文献类型：
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作者：
Li X;Xing YF;Lei AH;Xiao Q;Lin ZH;Hong YF;Wu XY;Zhou J
髓系来源的抑制细胞(MDSC)已被认为是治疗多种癌症的新靶点。然而，MDSC上的靶向药物并没有显示出令人满意的疗效。关键原因之一应该是不太理想的患者选择。在本研究中，我们的目标是确定与肝细胞癌患者MDSC水平相关的临床参数，为未来的MDSC靶向治疗提供依据。本研究分析了55例肝细胞癌患者(试验组)和20例健康献血者外周血单个核细胞(PBMC)中MDSC的频率。结果发现，与健康献血者相比，肝细胞癌患者mdsc水平升高(10.33%vs1.54%，p<；0.0001)。外周血单核细胞(R2=0.2875，P<0.0001)、中性粒细胞(R2=0.3630，P<0.0001)、血小板计数(R2=0.0828，P=0.0331)与MDSC水平呈正相关。然后，在255例肝细胞癌患者(验证组)的回顾性数据库中确定上述预测因素的预后价值。测试组和验证组的基线特征相似。多因素COX回归分析显示，中性粒细胞计数是总生存期(OS)的独立预测因素(P=0.000，HR 1.065，95%CI 1.028~1.103)，其余参数均未达到显著水平。综上所述，本研究首次确定血中中性粒细胞计数是预测肝细胞癌患者PBMC中MDSC水平的指标。中性粒细胞计数水平较高的患者可能是MDSC靶向治疗的最佳患者亚组。
Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p < 0.0001). The monocytes (r2 = 0.2875, p < 0.0001), neutrophils (r2 = 0.3630, p < 0.0001) and platelet counts (r2 = 0.0828, p = 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 255 HCC patients (validation group). The baseline characteristics of testing and validation group were similar. Multivariate analysis by Cox regression revealed that neutrophil count was an independent predictor for overall survival (OS) (p = 0.000, HR 1.065, 95% CI 1.028–1.103), with the rest parameters failed to reach a significant result. In summary, the present study firstly identified blood neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher neutrophil count level might be the optimal patient subgroup for MDSC targeted therapy.