Li Ji, Veltri Robert W, Yuan Zhen, Christudass Christhunesa S, Mandecki Wlodek
PharmaSeq, Inc., Monmouth Junction, New Jersey, United States of America.
Johns Hopkins University School of Medicine (JHUSOM), Baltimore, Maryland, United States of America.
PLoS One. 2015 Apr 8;10(4):e0122249. doi: 10.1371/journal.pone.0122249. eCollection 2015.
Prostate cancer (PCa) is the most common malignancy among men in the United States. Though highly sensitive, the often-used prostate-specific antigen (PSA) test has low specificity which leads to overdiagnosis and overtreatment of PCa. This paper presents results of a retrospective study that indicates that testing for macrophage inhibitory cytokine 1 (MIC-1) concentration along with the PSA assay could provide much improved specificity to the assay.
The MIC-1 serum level was determined by a novel p-Chip-based immunoassay run on 70 retrospective samples. The assay was configured on p-Chips, small integrated circuits (IC) capable of storing in their electronic memories a serial number to identify the molecular probe immobilized on its surface. The distribution of MIC-1 and pre-determined PSA concentrations were displayed in a 2D plot and the predictive power of the dual MIC-1/PSA assay was analyzed.
MIC-1 concentration in serum was elevated in PCa patients (1.44 ng/ml) compared to normal and biopsy-negative individuals (0.93 ng/ml and 0.88 ng/ml, respectively). In addition, the MIC-1 level was correlated with the progression of PCa. The area under the receiver operator curve (AUC-ROC) was 0.81 providing an assay sensitivity of 83.3% and specificity of 60.7% by using a cutoff of 0.494 for the logistic regression value of MIC-1 and PSA. Another approach, by defining high-frequency PCa zones in a two-dimensional plot, resulted in assay sensitivity of 78.6% and specificity of 89.3%.
The analysis based on correlation of MIC-1 and PSA concentrations in serum with the patient PCa status improved the specificity of PCa diagnosis without compromising the high sensitivity of the PSA test alone and has potential for PCa prognosis for patient therapy strategies.
前列腺癌(PCa)是美国男性中最常见的恶性肿瘤。尽管常用的前列腺特异性抗原(PSA)检测具有高度敏感性,但其特异性较低,这导致了前列腺癌的过度诊断和过度治疗。本文介绍了一项回顾性研究的结果,该研究表明,同时检测巨噬细胞抑制细胞因子1(MIC-1)浓度和PSA检测可以显著提高检测的特异性。
通过一种基于新型p芯片的免疫测定法测定70份回顾性样本中的MIC-1血清水平。该测定法配置在p芯片上,p芯片是一种小型集成电路(IC),能够在其电子存储器中存储序列号,以识别固定在其表面的分子探针。在二维图中显示MIC-1和预先确定的PSA浓度分布,并分析双MIC-1/PSA测定法的预测能力。
与正常人和活检阴性个体(分别为0.93 ng/ml和0.88 ng/ml)相比,前列腺癌患者血清中的MIC-1浓度升高(1.44 ng/ml)。此外,MIC-1水平与前列腺癌的进展相关。通过使用MIC-1和PSA的逻辑回归值的截断值0.494,受试者操作特征曲线(AUC-ROC)下的面积为0.81,测定法的灵敏度为83.3%,特异性为60.7%。另一种方法是在二维图中定义高频前列腺癌区域,其测定法的灵敏度为78.6%,特异性为89.3%。
基于血清中MIC-1和PSA浓度与患者前列腺癌状态的相关性分析,在不影响单独PSA检测高灵敏度的情况下提高了前列腺癌诊断的特异性,并且在患者治疗策略的前列腺癌预后方面具有潜力。