NDLI: Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

Content Provider	PubMed Central
Author	Nyberg, Fredrik Ogiwara, Atsushi Harbron, Chris G. Kawakami, Takao Nagasaka, Keiko Takami, Sachiko Wada, Kazuya Tu, Hsiao-kun Otsuji, Makiko Kyono, Yutaka Dobashi, Tae Komatsu, Yasuhiko Kihara, Makoto Akimoto, Shingo Peers, Ian S. South, Marie C. Tim, Higenbottam Fukuoka, Masahiro Nakata, Koichiro Ohe, Yuichiro Kudoh, Shoji Clausen, Ib Groth Nishimura, Toshihide György, Marko-varga Kato, Harubumi
Editor	Coonrod, Scott A.
Copyright Year	2011
Abstract	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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0022062
Starting Page	22062
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	7
Volume Number	6
Language	English
Publisher	Public Library of Science
Publisher Date	2011-07-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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