Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients
| العنوان: | Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients |
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| المؤلفون: | Shingo Akimoto, Kazuya Wada, Fredrik Nyberg, Ian Peers, Ib Groth Clausen, Keiko Nagasaka, Yuichiro Ohe, Marie C. South, Hsiao-kun Tu, Atsushi Ogiwara, Yutaka Kyono, Makoto Kihara, Makiko Otsuji, György Marko-Varga, Koichiro Nakata, Tim Higenbottam, Toshihide Nishimura, Harubumi Kato, Tae Dobashi, Takao Kawakami, Sachiko Takami, Chris Harbron, Masahiro Fukuoka, Yasuhiko Komatsu, Shoji Kudoh |
| المصدر: | PLoS ONE PLoS ONE, Vol 6, Iss 7, p e22062 (2011) |
| بيانات النشر: | Public Library of Science (PLoS), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Proteomics, Oncology, Lung Neoplasms, Proteome, Epidemiology, lcsh:Medicine, Bioinformatics, Biochemistry, Lung and Intrathoracic Tumors, Tandem Mass Spectrometry, Carcinoma, Non-Small-Cell Lung, lcsh:Science, Databases, Protein, Spectrometric Identification of Proteins, Multidisciplinary, Acute-phase protein, Interstitial lung disease, Discriminant Analysis, Gefitinib, respiratory system, Blood proteins, Phenotype, Medicine, Research Article, Cohort study, medicine.drug, Quality Control, Drugs and Devices, medicine.medical_specialty, Biology, Asian People, Diagnostic Medicine, Internal medicine, medicine, Carcinoma, Humans, Lung cancer, Pharmacoepidemiology, lcsh:R, Proteins, Cancers and Neoplasms, Reproducibility of Results, Acute Phase Proteins, medicine.disease, Non-Small Cell Lung Cancer, respiratory tract diseases, Quinazolines, lcsh:Q, Lung Diseases, Interstitial, Peptides, Biomarkers, Chromatography, Liquid |
| الوصف: | Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10(-25)), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4eada0c1912a69c682b0c7827fb82b31 https://doi.org/10.1371/journal.pone.0022062 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4eada0c1912a69c682b0c7827fb82b31 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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