Evaluation of a Serum Lung Cancer Biomarker Panel

Background: A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact o...

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Main Authors: Peter J Mazzone, Xiao-Feng Wang, Xiaozhen Han, Humberto Choi, Meredith Seeley, Richard Scherer, Victoria Doseeva
Format: Article
Language:English
Published: SAGE Publishing 2018-01-01
Series:Biomarker Insights
Online Access:https://doi.org/10.1177/1177271917751608
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author Peter J Mazzone
Xiao-Feng Wang
Xiaozhen Han
Humberto Choi
Meredith Seeley
Richard Scherer
Victoria Doseeva
author_facet Peter J Mazzone
Xiao-Feng Wang
Xiaozhen Han
Humberto Choi
Meredith Seeley
Richard Scherer
Victoria Doseeva
author_sort Peter J Mazzone
collection DOAJ
description Background: A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. Methods: The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. Results: The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. Conclusions: This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results.
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spelling doaj.art-31b3196302f942978606e85056290e242022-12-22T01:20:38ZengSAGE PublishingBiomarker Insights1177-27192018-01-011310.1177/1177271917751608Evaluation of a Serum Lung Cancer Biomarker PanelPeter J Mazzone0Xiao-Feng Wang1Xiaozhen Han2Humberto Choi3Meredith Seeley4Richard Scherer5Victoria Doseeva6Respiratory Institute, Cleveland Clinic, Cleveland, OH, USADepartment of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USADepartment of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USARespiratory Institute, Cleveland Clinic, Cleveland, OH, USARespiratory Institute, Cleveland Clinic, Cleveland, OH, USA20/20 GeneSystems, Rockville, MD, USA20/20 GeneSystems, Rockville, MD, USABackground: A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. Methods: The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. Results: The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. Conclusions: This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results.https://doi.org/10.1177/1177271917751608
spellingShingle Peter J Mazzone
Xiao-Feng Wang
Xiaozhen Han
Humberto Choi
Meredith Seeley
Richard Scherer
Victoria Doseeva
Evaluation of a Serum Lung Cancer Biomarker Panel
Biomarker Insights
title Evaluation of a Serum Lung Cancer Biomarker Panel
title_full Evaluation of a Serum Lung Cancer Biomarker Panel
title_fullStr Evaluation of a Serum Lung Cancer Biomarker Panel
title_full_unstemmed Evaluation of a Serum Lung Cancer Biomarker Panel
title_short Evaluation of a Serum Lung Cancer Biomarker Panel
title_sort evaluation of a serum lung cancer biomarker panel
url https://doi.org/10.1177/1177271917751608
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