Trivedi Neil N, Brown James K, Rubenstein Tess, Rostykus Abigail D, Fish Amanda L, Yu Heng, Carbonell Luis, Juang Alice, Kamer Sandy, Patel Bhavin, Sidhu Manpreet, Vuong Doris, Wang Shan, Beggs Mike, Wu Alan Hb, Arjomandi Mehrdad
San Francisco Veterans Affairs Medical Center, USA.
MagArray Inc, Milpitas, CA, USA.
Biomed Res Rev. 2018 Dec;2(3). doi: 10.15761/brr.1000123. Epub 2018 Nov 23.
In the National Lung Screening Trial, 96.4% of nodules had benign etiology. To avoid unnecessary actions and exposure to harm, individuals with benign disease must be identified. We describe herein the analytical validation of a multi-analyte immunoassay for characterizing the risk that a lung nodule found on CT is malignant. Those at lower risk may be considered for serial surveillance to avoid unnecessary and potentially harmful procedures. While those nodules characterized at higher risk may be appropriate for more aggressive actions.
To validate the analytical performance of multiplexed plasma protein assays used in a novel test for lung nodule characterization.
A multiplexed immunoassay panel for the measurement of plasma proteins in current smokers who present with a lung nodule on CT scan was evaluated in a clinical testing laboratory. Assay analytical sensitivity, reproducibility, precision, and recovery of Epidermal Growth Factor Receptor (EGFR), Prosurfactant protein B (ProSB), and Tissue Inhibitor of Metalloproteinases 1 (TIMP1) from human EDTA plasma samples were evaluated across multiple runs, lots, and technicians. Interfering substances and sample pre-analytical storage conditions were evaluated for their effect on analyte recovery. The lung nodule risk score reproducibility was assessed across multiple lots.
The assay sensitivities were 0.10 ng/mL EGFR, 0.02 ng/mL ProSB, and 0.29 ng/mL TIMP1 with over three orders of magnitude in the assay dynamic ranges. The assays and analytes are robust to pre-analytical sample handling and the plasma can be stored for up to 4 days at 4°C either when freshy collected or thawed after long-term storage at -80°C. Total imprecision after 20 days of testing remained under 9% for all three assays. Risk score variability remained within a ± 10% risk score range.
The three protein assays comprising the multi-analyte plasma test for lung nodule characterization performed quite acceptably in a clinical laboratory.
在国家肺癌筛查试验中，96.4%的结节病因良性。为避免不必要的措施和有害暴露，必须识别患有良性疾病的个体。我们在此描述一种多分析物免疫测定法的分析验证，该方法用于表征CT上发现的肺结节为恶性的风险。风险较低者可考虑进行连续监测，以避免不必要的、可能有害的程序。而那些风险较高的结节可能适合采取更积极的措施。
验证用于肺结节特征化新检测方法中的多重血浆蛋白测定法的分析性能。
在临床检测实验室中，对用于测量CT扫描显示有肺结节的现吸烟者血浆蛋白的多重免疫测定面板进行了评估。在多次运行、批次和技术人员中，评估了人EDTA血浆样本中表皮生长因子受体（EGFR）、表面活性蛋白B前体（ProSB）和基质金属蛋白酶1组织抑制剂（TIMP1）的测定分析灵敏度、重现性、精密度和回收率。评估了干扰物质和样本分析前储存条件对分析物回收率的影响。在多个批次中评估了肺结节风险评分的重现性。
测定灵敏度分别为EGFR 0.10 ng/mL、ProSB 0.02 ng/mL和TIMP1 0.29 ng/mL，测定动态范围超过三个数量级。这些测定法和分析物对分析前样本处理具有稳健性，新鲜采集的血浆或在-80°C长期储存后解冻的血浆在4°C下可储存长达4天。所有三种测定法在测试20天后的总不精密度仍低于9%。风险评分变异性保持在风险评分范围的±10%以内。
用于肺结节特征化的多分析物血浆检测中的三种蛋白质测定法在临床实验室中的表现相当令人满意。
