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

Shaun Daly, Daniel Rinewalt, Cristina Fhied, Sanjib Basu, Brett Mahon, Michael J. Liptay, Edward Hong, Gary Chmielewski, Mark A. Yoder, Palmi N. Shah, Eric S. Edell, Fabien Maldonado, Aaron O. Bungum, Jeffrey A. Borgia

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)31-36
Number of pages6
JournalJournal of Thoracic Oncology
Volume8
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Low-dose computed tomography screening
  • Lung cancer
  • Nodules
  • Plasma biomarkers
  • Validation

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Daly, S., Rinewalt, D., Fhied, C., Basu, S., Mahon, B., Liptay, M. J., Hong, E., Chmielewski, G., Yoder, M. A., Shah, P. N., Edell, E. S., Maldonado, F., Bungum, A. O., & Borgia, J. A. (2013). Development and validation of a plasma biomarker panel for discerning clinical significance of indeterminate pulmonary nodules. Journal of Thoracic Oncology, 8(1), 31-36. https://doi.org/10.1097/JTO.0b013e31827627f8