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CD163+CD14+巨噬细胞,一种恶性胸腔积液潜在的免疫生物标志物。

CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion.

作者信息

Wang Fei, Yang Li, Gao Qun, Huang Lan, Wang Liping, Wang Jing, Wang Shengdian, Zhang Bin, Zhang Yi

机构信息

Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, China.

出版信息

Cancer Immunol Immunother. 2015 Aug;64(8):965-76. doi: 10.1007/s00262-015-1701-9. Epub 2015 May 6.

Abstract

BACKGROUND

Malignant pleural effusion (MPE) is a common complication caused by malignant diseases. However, subjectivity, poor sensitivity, and substantial false-negative rates of cytology assay hamper accurate MPE diagnosis. The aim of this study was to assess whether CD163+CD14+ tumor-associated macrophages (TAMs) could be used as a biomarker for enabling sensitive and specific MPE diagnosis.

METHODS

Pleural effusion samples and peripheral blood samples were collected from 50 MPE patients and 50 non-malignant pleural effusion (NMPE) patients, respectively. Flow cytometry was performed to analyze cell phenotypes, and RT-qPCR was used to detect cytokine expression in these monocytes and macrophages. A blinded validation study (n = 40) was subsequently performed to confirm the significance of CD163+CD14+ TAMs in MPE diagnosis. Student's t test, rank sum test, and receiver operating characteristic curve analysis were used for statistical analysis.

RESULTS

Notably, CD163+CD14+ cell frequency in MPE was remarkably higher than that in NMPE (P < 0.001). In a blinded validation study, a sensitivity of 78.9 % and a specificity of 100 % were obtained with CD163+CD14+ TAMs as a MPE biomarker. In total (n = 140), by using a cutoff level of 3.65 %, CD163+CD14+ cells had a sensitivity of 81.2 % and a specificity of 100 % for MPE diagnosis. Notably, MPE diagnosis by estimating CD163+CD14+ cells in pleural effusion could be obtained one week earlier than that obtained by cytological examination.

CONCLUSIONS

CD163+CD14+ macrophages could be potentially used as an immune diagnostic marker for MPE and has better assay sensitivity than that of cytological analysis.

摘要

背景

恶性胸腔积液(MPE)是恶性疾病引起的常见并发症。然而,细胞学检测的主观性、低敏感性和较高的假阴性率阻碍了MPE的准确诊断。本研究旨在评估CD163+CD14+肿瘤相关巨噬细胞(TAMs)是否可作为一种生物标志物用于敏感且特异的MPE诊断。

方法

分别从50例MPE患者和50例非恶性胸腔积液(NMPE)患者中采集胸腔积液样本和外周血样本。采用流式细胞术分析细胞表型,并用RT-qPCR检测这些单核细胞和巨噬细胞中的细胞因子表达。随后进行了一项盲法验证研究(n = 40),以确认CD163+CD14+ TAMs在MPE诊断中的意义。采用学生t检验、秩和检验和受试者工作特征曲线分析进行统计分析。

结果

值得注意的是,MPE中CD163+CD14+细胞频率显著高于NMPE(P < 0.001)。在一项盲法验证研究中,以CD163+CD14+ TAMs作为MPE生物标志物时,敏感性为78.9%,特异性为100%。总共(n = 140),采用3.65%的截断水平时,CD163+CD14+细胞对MPE诊断的敏感性为81.2%,特异性为100%。值得注意的是,通过估计胸腔积液中CD163+CD14+细胞进行MPE诊断比细胞学检查早一周。

结论

CD163+CD14+巨噬细胞可能作为MPE的免疫诊断标志物,且比细胞学分析具有更好的检测敏感性。

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