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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-3
pubmed:abstractText
Targeted glycoproteomics represents an attractive approach for conducting peripheral blood based cancer biomarker discovery due to the well-known altered pattern of protein glycosylation in cancer and the reduced complexity of the resultant glycoproteome. Here we report its application to a set of pooled nonsmall cell lung cancer (NSCLC) case sera (9 adenocarcinoma and 6 squamous cell carcinoma pools from 54 patients) and matched controls pools, including 8 clinical control pools with computed tomography detected nodules but being nonmalignant as determined by biopsy from 54 patients, and 8 matched healthy control pools from 106 cancer-free subjects. The goal of the study is to discover biomarkers that may enable improved early detection and diagnosis of lung cancer. Immunoaffinity subtraction was used to first deplete the topmost abundant serum proteins; the remaining serum proteins were then subjected to hydrazide chemistry based glycoprotein capture and enrichment. Hydrazide resin in situ trypsin digestion was used to release nonglycosylated peptides. Formerly N-linked glycosylated peptides were released by peptide-N-glycosidase F (PNGase F) treatment and were subsequently analyzed by liquid chromatography (LC)-tandem mass spectrometry (MS/MS). A MATLAB based in-house tool was developed to facilitate retention time alignment across different LC-MS/MS runs, determination of precursor ion m/z values and elution profiles, and the integration of mass chromatograms based on determined parameters for identified peptides. A total of 38 glycopeptides from 22 different proteins were significantly differentially abundant across the case/control pools (P < 0.01, Student's t test) and their abundances led to a near complete separation of case and control pools based on hierarchical clustering. The differential abundances of three of these candidate proteins were verified by commercially available ELISAs applied in the pools. Strong positive correlations between glycopeptide mass chromatograms and ELISA-measured protein abundance was observed for all of the selected glycoproteins.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1535-3907
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6440-9
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed-meshheading:20931982-Adenocarcinoma, pubmed-meshheading:20931982-Aged, pubmed-meshheading:20931982-Amino Acid Sequence, pubmed-meshheading:20931982-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:20931982-Carcinoma, Squamous Cell, pubmed-meshheading:20931982-Chromatography, Liquid, pubmed-meshheading:20931982-Cluster Analysis, pubmed-meshheading:20931982-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:20931982-Female, pubmed-meshheading:20931982-Glycopeptides, pubmed-meshheading:20931982-Glycoproteins, pubmed-meshheading:20931982-Humans, pubmed-meshheading:20931982-Lung Neoplasms, pubmed-meshheading:20931982-Male, pubmed-meshheading:20931982-Middle Aged, pubmed-meshheading:20931982-Molecular Sequence Data, pubmed-meshheading:20931982-Proteomics, pubmed-meshheading:20931982-Tandem Mass Spectrometry, pubmed-meshheading:20931982-Tumor Markers, Biological
pubmed:year
2010
pubmed:articleTitle
Lung cancer serum biomarker discovery using glycoprotein capture and liquid chromatography mass spectrometry.
pubmed:affiliation
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural