Development of an AlphaLISA assay to quantify serum core-fucosylated E-cadherin as a metastatic lung adenocarcinoma biomarker
Journal
Journal of Proteomics
Journal Volume
75
Journal Issue
13
Pages
3963-3976
Date Issued
2012
Author(s)
Abstract
Lung cancer is the leading cause of cancer-associated deaths worldwide. Non-small cell lung cancer is a heterogeneous condition with variability in prognosis and in individual response to treatment. Thus, the identification of patients with a high risk of metastasis or relapse after surgery would allow better management. There is increasing evidence that glycosylation plays a significant role in biological processes including oncogenic transformation and metastasis. We set up a platform to screen and identify serum glycoproteins as metastasis biomarkers of lung cancer. Concanavalin A affinity chromatography was used to enrich glycoproteins from pooled serum of lung adenocarcinoma patients. The captured glycoproteins were separated with 2-D DIGE combined with nano-LC-MS/MS and identified by database searching. Some differentially expressed cancer-related glycoproteins, such as α-1-antitrypsin, complement C3c, haptoglobin, and E-cadherin, were identified. These glycoproteins were evaluated by Western blotting and Aleuria aurantia lectin staining and several, including E-cadherin, showed increased core-fucosylation during lung cancer progression. We then measured the fucosylation index (FI) of E-cadherin in 154 lung adenocarcinoma patients. In addition, a homogeneous proximity-based AlphaLISA assay to measure the FI of E-cadherin was established. The present study indicates that the FI of E-cadherin could be a potential prognostic marker of metastatic lung adenocarcinoma. ? 2012 Elsevier B.V.
SDGs
Other Subjects
alpha 1 antitrypsin; alpha 2 macroglobulin; apolipoprotein A1; biological marker; complement component C3c; complement component C4a; concanavalin A; fibrinogen; haptoglobin; lectin; protein precursor; serum amyloid P; uvomorulin; adult; affinity chromatography; aged; article; assay; cancer prognosis; controlled study; female; fucosylation; fucosylation index; high throughput screening; human; liquid chromatography; lung adenocarcinoma; major clinical study; male; malignant transformation; mass spectrometry; metastasis; nucleotide sequence; priority journal; protein determination; protein expression; reproducibility; staining; survival rate; two dimensional difference gel electrophoresis; Western blotting; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Cadherins; Carcinoma, Non-Small-Cell Lung; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Humans; Lung Neoplasms; Male; Middle Aged; Tumor Markers, Biological; Aleuria aurantia
Type
journal article