Establishment of a Multi-Analyte Serum Biomarker Panel to Identify Lymph Node Metastases in Non-small Cell Lung Cancer Jeffrey A. Borgia, PhD, Sanjib.

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Establishment of a Multi-Analyte Serum Biomarker Panel to Identify Lymph Node Metastases in Non-small Cell Lung Cancer Jeffrey A. Borgia, PhD, Sanjib Basu, PhD, L Penfield Faber, MD, Anthony W. Kim, MD, John S. Coon, MD, PhD, Kelly A. Kaiser-Walters, BS, Cristina Fhied, MS, Sherene Thomas, PhD, Omid Rouhi, MD, William H. Warren, MD, Philip Bonomi, MD, Michael J. Liptay, MD Journal of Thoracic Oncology Volume 4, Issue 3, Pages 338-347 (March 2009) DOI: 10.1097/JTO.0b013e3181982abf Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Boxplots of biomarker candidates from the Random Forest analysis. Box and Whisker plots were generated for each individual biomarker in the final iteration of the Random Forest analysis. Designations on the abscissa: “0” refers to lymph node negative, whereas “1” refers to lymph node positive (both relative to pathologic stage). The extreme values are hidden. Journal of Thoracic Oncology 2009 4, 338-347DOI: (10.1097/JTO.0b013e3181982abf) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Classification and Regression Tree for predicting preoperative nodal status in non-small cell lung cancer (NSCLC) patients. A binary ‘if-then’ set of decision rules is used to split the data into separate branches of the tree with each node of the tree displaying the appropriate analyte and threshold concentrations. Additional classifications continue to the left if the threshold is not met, and to the right if the value is equal to or exceeding this cutoff. The number of classifications (observations) are listed immediately below each terminal node, with each final arm labeled (0 = node negative; 1 = node positive). Journal of Thoracic Oncology 2009 4, 338-347DOI: (10.1097/JTO.0b013e3181982abf) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Receiver operator characteristic curve for the most robust staging subpanel generated by the Random Forest analysis. Area under the curve = 0.94; Sensitivity = 88%; Specificity = 87%. Journal of Thoracic Oncology 2009 4, 338-347DOI: (10.1097/JTO.0b013e3181982abf) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 Boxplots of the 6-analyte biomarker panel for identifying preoperative nodal status with respect to extent of nodal station involvement. Boxplots for the 6-analytes comprising our most optimal panel for predicting lymph node involvement are represented with the node positive subjects subdivided according to either single or multiple nodal station involvement as a surrogate for total nodal involvement. (Mann-Whitney p-values: *, p = 0.011; **, p = 0.07; **, p = 0.012). Journal of Thoracic Oncology 2009 4, 338-347DOI: (10.1097/JTO.0b013e3181982abf) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions