Development of an AlphaLISA assay to quantify serum core-fucosylated E-cadherin as a metastatic lung adenocarcinoma biomarker.
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.
Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan. f91442007@ntu.edu.tw
Chu-Ling
CL
Wen
Kuan-Yu
KY
Chen
Chih-Ta
CT
Chen
Jiing-Guang
JG
Chuang
Pan-Chyr
PC
Yang
Lu-Ping
LP
Chow
D000230:Adenocarcinoma / Q000097:blood* / Q000737:chemistry / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D015820:Cadherins / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged
D014408:Biomarkers, Tumor; D015820:Cadherins; D006023:Glycoproteins