Development and validation of a plasma biomarker panel for discerning clinical significance of indeterminate pulmonary nodules.

Daly S, Rinewalt D, Fhied C, Basu S, Mahon B, Liptay MJ, Hong E, Chmielewski G, Yoder MA, Shah PN, Edell ES, Maldonado F, Bungum AO, Borgia JA
J Thorac Oncol. 2013 8 (1): 31-6

PMID: 23201823 · DOI:10.1097/JTO.0b013e31827627f8

INTRODUCTION - The recent findings of the National Lung Screening Trial showed 24.2% of individuals at high risk for lung cancer having one or more indeterminate nodules detected by low-dose computed tomography-based screening, 96.4% of which were eventually confirmed as false positives. These positive scans necessitate additional diagnostic procedures to establish a definitive diagnosis that adds cost and risk to the paradigm. A plasma test able to assign benign versus malignant pathology in high-risk patients would be an invaluable tool to complement low-dose computed tomography-based screening and promote its rapid implementation.

METHODS - We evaluated 17 biomarkers, previously shown to have value in detecting lung cancer, against a discovery cohort, comprising benign (n = 67) cases and lung cancer (n = 69) cases. A Random Forest method based analysis was used to identify the optimal biomarker panel for assigning disease status, which was then validated against a cohort from the Mayo Clinic, comprising patients with benign (n = 61) or malignant (n = 20) indeterminate lung nodules.

RESULTS - Our discovery efforts produced a seven-analyte plasma biomarker panel consisting of interleukin 6 (IL-6), IL-10, IL-1ra, sIL-2Rα, stromal cell-derived factor-1α+β, tumor necrosis factor α, and macrophage inflammatory protein 1 α. The sensitivity and specificity of our panel in our validation cohort is 95.0% and 23.3%, respectively. The validated negative predictive value of our panel was 93.8%.

CONCLUSION - We developed a seven-analyte plasma biomarker panel able to identify benign nodules, otherwise deemed indeterminate, with a high degree of accuracy. This panel may have clinical utility in risk-stratifying screen-detected lung nodules, decrease unnecessary follow-up imaging or invasive procedures, and potentially avoid unnecessary morbidity, mortality, and health care costs.

MeSH Terms (27)

Adult Aged Aged, 80 and over Area Under Curve Biomarkers, Tumor Chemokine CCL3 Chemokine CXCL12 Cytokines Female Granuloma Humans Interleukin-2 Receptor alpha Subunit Interleukin-6 Interleukin-10 Interleukin 1 Receptor Antagonist Protein Lung Neoplasms Male Middle Aged Multiple Pulmonary Nodules Pneumonia Predictive Value of Tests Radiography Respiratory Tract Infections ROC Curve Solitary Pulmonary Nodule Tumor Necrosis Factor-alpha Young Adult

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