Wang Fei, Yang Li, Gao Qun, Huang Lan, Wang Liping, Wang Jing, Wang Shengdian, Zhang Bin, Zhang Yi
Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, China.
Cancer Immunol Immunother. 2015 Aug;64(8):965-76. doi: 10.1007/s00262-015-1701-9. Epub 2015 May 6.
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.
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.
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.
CD163+CD14+ macrophages could be potentially used as an immune diagnostic marker for MPE and has better assay sensitivity than that of cytological analysis.
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。
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。
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。
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。