Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool
| العنوان: | Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool |
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| المؤلفون: | Stephen Levin, Michael R. Mehan, Brad Black, Edward N. Brody, Stephen A. Williams, Deborah Ayers, Harvey I. Pass, Michael Harbut, Michele Carbone, Chandra Goparaju, Alex Stewart, Rachel Ostroff |
| المصدر: | PLoS ONE, Vol 7, Iss 10, p e46091 (2012) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Mesothelioma, Proteomics, Oncology, Pathology, Pulmonology, Epidemiology, lcsh:Medicine, Lung and Intrathoracic Tumors, Cohort Studies, 0302 clinical medicine, Lectins, Public Health Surveillance, Biomarker discovery, lcsh:Science, Aged, 80 and over, Principal Component Analysis, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, Middle Aged, Pleural Diseases, 3. Good health, 030220 oncology & carcinogenesis, Asbestosis, Medicine, Female, Cancer Screening, Research Article, Test Evaluation, Cohort study, Adult, medicine.medical_specialty, Pleural Neoplasms, Population, Enzyme-Linked Immunosorbent Assay, Environmental and Occupational Lung Diseases, Malignancy, Sensitivity and Specificity, Young Adult, 03 medical and health sciences, Diagnostic Medicine, Internal medicine, Biomarkers, Tumor, Cancer Detection and Diagnosis, Early Detection, medicine, Humans, Mesothelin, Pleural Neoplasm, education, Aged, 030304 developmental biology, business.industry, lcsh:R, Case-control study, Reproducibility of Results, Cancers and Neoplasms, Asbestos, medicine.disease, Biomarker Epidemiology, Case-Control Studies, Carcinogens, biology.protein, lcsh:Q, business, Biomarkers, General Pathology |
| الوصف: | Background: Malignant pleural mesothelioma (MM) is an aggressive, asbestos-related pulmonary cancer that is increasing in incidence. Because diagnosis is difficult and the disease is relatively rare, most patients present at a clinically advanced stage where possibility of cure is minimal. To improve surveillance and detection of MM in the high-risk population, we completed a series of clinical studies to develop a noninvasive test for early detection. Methodology/Principal Findings: We conducted multi-center case-control studies in serum from 117 MM cases and 142 asbestos-exposed control individuals. Biomarker discovery, verification, and validation were performed using SOMAmer proteomic technology, which simultaneously measures over 1000 proteins in unfractionated biologic samples. Using univariate and multivariate approaches we discovered 64 candidate protein biomarkers and derived a 13-marker random forest classifier with an AUC of 0.9960.01 in training, 0.9860.04 in independent blinded verification and 0.9560.04 in blinded validation studies. Sensitivity and specificity at our pre-specified decision threshold were 97%/92% in training and 90%/95% in blinded verification. This classifier accuracy was maintained in a second blinded validation set with a sensitivity/ specificity of 90%/89% and combined accuracy of 92%. Sensitivity correlated with pathologic stage; 77% of Stage I, 93% of Stage II, 96% of Stage III and 96% of Stage IV cases were detected. An alternative decision threshold in the validation study yielding 98% specificity would still detect 60% of MM cases. In a paired sample set the classifier AUC of 0.99 and 91%/94% sensitivity/specificity was superior to that of mesothelin with an AUC of 0.82 and 66%/88% sensitivity/specificity. The candidate biomarker panel consists of both inflammatory and proliferative proteins, processes strongly associated with asbestos-induced malignancy. Significance: The SOMAmer biomarker panel discovered and validated in these studies provides a solid foundation for surveillance and diagnosis of MM in those at highest risk for this disease. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::932d77e861b5bf69239535d45085a2dd http://europepmc.org/articles/PMC3463527?pdf=render |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....932d77e861b5bf69239535d45085a2dd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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