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A novel serum based biomarker panel has complementary ability to preclude presence of early lung cancer for low dose CT (LDCT).

ABSTRACT: Low Dosage Computerized Tomography (LDCT) has been shown to improve early detection of lung cancer and mortality rates in high-risk individuals, which was, however, limited by specifically coverage for heavy smokers and high rates of false positivity. Here, we aim to investigate a novel biomarker for early detection of lung cancer, and further extend to concentrate high-risk subjects for increasing specificity and coverage of LDCT. We performed retrospective blinded evaluation of lung cancer and healthy controls in training and validation cohorts. Macrophage inhibitory cytokine 1 (MIC-1) alone and panel were assessed. Our data showed the sensitivity of MIC-1 was 72.2% and 67.1% for lung cancer diagnosis and early diagnosis respectively, at 96.6% specificity, which were significantly higher than Cyfra21-1, NSE CA125, CEA and SCC. At 90% specificity, the panel of MIC-1, Cyfra21-1, CA125 and CEA provided 89.5% sensitivity for early diagnosis of lung cancer, which could be used to concentrate the high-risk subjects for further LDCT screening. We conclude that MIC-1 have great capacity in early lung cancer diagnosis. The algorithmic panel of MIC-1, Cyfra21-1, CA125 and CEA could be used to refine the preselection criteria of high-risk subjects, and thus might facilitate the widespread implementation of LDCT screening.

SUBMITTER: Wang X

PROVIDER: S-EPMC5542191 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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A novel serum based biomarker panel has complementary ability to preclude presence of early lung cancer for low dose CT (LDCT).

Wang Xiaobing X Zhi Xiuyi X Yang Zhaogang Z Tian Haimei H Li Yanfen Y Li Mo M Zhao Wenya W Zhang Chao C Wang Teng T Liu Jing J Shen Di D Zheng Cuining C Zhao Dan D Yang Sheng S Qi Jun J Xin Hongwu H Stojadinovic Alexander A Avital Itzhak I Lee L James LJ Rao Jianyu J Zhang Wei W

Oncotarget 20170701 28

Low Dosage Computerized Tomography (LDCT) has been shown to improve early detection of lung cancer and mortality rates in high-risk individuals, which was, however, limited by specifically coverage for heavy smokers and high rates of false positivity. Here, we aim to investigate a novel biomarker for early detection of lung cancer, and further extend to concentrate high-risk subjects for increasing specificity and coverage of LDCT. We performed retrospective blinded evaluation of lung cancer and ...[more]

PMID: 28514755

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Project description:IntroductionClinical decision making in the setting of computed tomography (CT) screening could benefit from accessible biomarkers that help predict the level of lung cancer risk in high-risk individuals with indeterminate pulmonary nodules.MethodsTo identify candidate serum biomarkers, we measured 70 cancer-related proteins by Luminex xMAP (Luminex Corporation) multiplexed immunoassays in a training set of sera from 56 patients with biopsy-proven primary non-small-cell lung cancer and 56 age-, sex-, and smoking-matched CT-screened controls.ResultsWe identified a panel of 10 serum biomarkers-prolactin, transthyretin, thrombospondin-1, E-selectin, C-C motif chemokine 5, macrophage migration inhibitory factor, plasminogen activator inhibitor, receptor tyrosine-protein kinase, erbb-2, cytokeratin fragment 21.1, and serum amyloid A-that distinguished lung cancer patients from controls with an estimated balanced accuracy (average of sensitivity and specificity) of 76.0 ± 3.8% from 20-fold internal cross-validation. We then iteratively evaluated this model in an independent test and verification case/control studies confirming the initial classification performance of the panel. The classification performance of the 10-biomarker panel was also analytically validated using enzyme-linked immunosorbent assays in a second independent case/control population, further validating the robustness of the panel.ConclusionsThe performance of this 10-biomarker panel-based model was 77.1% sensitivity/76.2% specificity in cross-validation in the expanded training set, 73.3% sensitivity/93.3% specificity (balanced accuracy 83.3%) in the blinded verification set with the best discriminative performance in stage I/II cases: 85% sensitivity (balanced accuracy 89.2%). Importantly, the rate of misclassification of CT-screened controls was not different in most control subgroups with or without airflow obstruction or emphysema or pulmonary nodules. These biomarkers have potential to aid in the early detection of lung cancer and more accurate interpretation of indeterminate pulmonary nodules detected by CT screening.

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A novel serum based biomarker panel has complementary ability to preclude presence of early lung cancer for low dose CT (LDCT).

Publications

A novel serum based biomarker panel has complementary ability to preclude presence of early lung cancer for low dose CT (LDCT).

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