LungLife AI, Inc., 2545 W. Hillcrest Drive, Suite 140, Thousand Oaks, CA, 91320, USA.
Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
BMC Pulm Med. 2024 Sep 27;24(1):475. doi: 10.1186/s12890-024-03280-7.
Evaluation of indeterminate pulmonary nodules (IPNs) often creates a diagnostic conundrum which may delay the early detection of lung cancer. Rare circulating genetically abnormal cells (CGAC) have previously demonstrated utility as a biomarker for discriminating benign from malignant small IPNs in the LungLB assay. CGAC are identified using a unique 4-color fluorescence in-situ hybridization (FISH) assay and are thought to reflect early cell-based events in lung cancer pathogenesis and the anti-tumor immune response. LungLB is a prognostic tool that combines the CGAC biomarker and clinical features to aid in IPN evaluation by improving the stratification of patient risk of malignancy.
Herein we describe the analytical performance of the LungLB blood test. Analytical validation was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines with adaptations for rare cell-based assays. Multiple operators, reagent lots, and assay runs were tested to examine accuracy, precision, reproducibility, and interfering factors.
The FISH probes used in the LungLB assay demonstrate 100% sensitivity and specificity for their intended chromosomal loci (3q29, 3p22.1, 10q22.3 and 10cen). LungLB demonstrates analytical sensitivity of 10 CGAC per 10,000 lymphocytes analyzed, 100% analytical specificity, and high linearity (R = 0.9971). Within run measurements across 100 samples demonstrated 96% reproducibility. Interfering factors normally found in blood (lipemia, biotin) and exposure to adverse temperatures (-20ºC or 37ºC) did not interfere with results. Sample stability was validated to 96 hours.
The analytical performance of LungLB in this validation study successfully demonstrates it is robust and suitable for everyday clinical use.
对肺部不确定结节（IPN）的评估常常会造成诊断上的困惑，从而可能延迟肺癌的早期发现。罕见的循环遗传异常细胞（CGAC）先前已被证明可作为区分 LungLB 检测中良性和恶性小 IPN 的生物标志物。CGAC 是通过使用独特的 4 色荧光原位杂交（FISH）检测来识别的，被认为反映了肺癌发病机制和抗肿瘤免疫反应中的早期基于细胞的事件。LungLB 是一种预后工具，它结合了 CGAC 生物标志物和临床特征，通过改善患者恶性肿瘤风险的分层来辅助 IPN 评估。
在此，我们描述了 LungLB 血液检测的分析性能。根据临床和实验室标准协会（CLSI）指南进行了分析验证，并针对稀有基于细胞的检测进行了调整。对多个操作人员、试剂批次和检测运行进行了测试，以检查准确性、精密度、重现性和干扰因素。
LungLB 检测中使用的 FISH 探针对其预期的染色体位点（3q29、3p22.1、10q22.3 和 10cen）具有 100%的灵敏度和特异性。LungLB 显示出 10 CGAC 分析每 10,000 个淋巴细胞的分析灵敏度，100%的分析特异性和高线性度（R=0.9971）。在 100 个样本的运行内测量中，重现性为 96%。通常在血液中发现的干扰因素（脂血症、生物素）和暴露于不利温度（-20°C 或 37°C）不会干扰结果。对样本稳定性进行了验证，结果可稳定 96 小时。
在这项验证研究中，LungLB 的分析性能成功地证明了它是强大的，适合日常临床使用。
