Analytical Validation of a Laboratory-Developed Lung Nodule Risk Reclassifier Assay.

BACKGROUND: Lung cancer is the second leading cause of death in the United States. Lung cancer is often diagnosed in its late stage leading to a poor prognosis. Lung nodules are often described as indeterminate from CT scans resulting in lung biopsies that are invasive and may lead to complications. The need for noninvasive methods to assess malignancy risk in lung nodules is great. METHODS: The lung nodule risk reclassifier assay consists of 7 protein biomarkers: Carcinoembryonic Antigen (CEA), C-X-C Motif Chemokine Ligand 10 (CXCL10), Epidermal Growth Factor Receptor (EGFR), Neutrophil Activating Protein-2 (NAP2), Pro-surfactant Protein B (ProSB), Receptor for Advanced Glycation Endproducts (RAGE), and Tissue Inhibitor of Metalloproteinase Inhibitor 1 (TIMP1) and 6 clinical factors (subject age, smoking pack years, and sex, and lung nodule size, location, and spiculated appearance). The protein biomarker assays comprise a multiplex immunoassay panel printed on giant magnetoresistance (GMR) sensor chips as components of a printed circuit board (PCB) run on the MagArray MR-813 instrument system. The analytical validation consisted of imprecision, accuracy, linearity, limits of blank, and limits of detection studies for each biomarker. Several reagents, as well as PCBs, were used in these studies. The entire validation study also assessed multiple users. RESULTS: This laboratory-developed test (LDT), using the MagArray platform, meets the manufacturer's specifications for imprecision, analytical sensitivity, linearity, and recovery. Common biological interferents are known to interfere with the detection of each biomarker. CONCLUSIONS: The lung nodule risk reclassifier assay performed as required to be offered as an LDT in the MagArray CLIA-certified laboratory.