Galectin-3 and S100A9: Novel diabetogenic factors mediating pancreatic cancer-associated diabetes
Journal
Diabetes Care
Journal Volume
42
Journal Issue
9
Pages
1752-1759
Date Issued
2019
Author(s)
Huang B.-S.
Yu Y.-H.
Yang H.-H.
Chen P.-R.
Huang C.-C.
Huang H.-Y.
Abstract
OBJECTIVE Pancreatic cancer-associated diabetes (PCDM) is a paraneoplastic phenomenon accounting for 1% of new-onset diabetes.We aimed to identify themediators of PCDM and evaluate their usefulness in distinguishing PCDM from type 2 diabetes. RESEARCH DESIGN AND METHODS Secreted proteins of MIA PaCa-2 cells were identified by proteomics, and those with ?10-fold overexpression in transcriptome analysis were assessed by bioinformatics and glucose uptake assay to identify candidate factors. Expression of factors was compared between tumors with and without PCDM by immunohistochemistry. Serum levels were measured in a training set including PC with and without PCDM, type 2 diabetes, pancreatitis, other pancreatic/peripancreatic tumors, and control subjects (n = 50 each). Cutoff values for differentiation between PCDM and type 2 diabetes from the training set were validated in a test set (n = 41 each). RESULTS Galectin-3 and S100A9 were overexpressed in tumors with PCDM and dosedependently suppressed insulin-stimulated glucose uptake in C2C12 myotubes. In the training set, serum galectin-3 and S100A9 levels were exclusively increased in patients with PCDM and distinguished PCDM from type 2 diabetes (area under the curve [AUC] galectin-3: 0.73 [95% CI 0.64-0.83]; S100A9: 0.79 [95% CI 0.70-0.87]). Similar results were observed in the test set (AUC galectin-3: 0.83 [95% CI 0.74-0.92]; S100A9: 0.77 [95% CI 0.67-0.87]), with sensitivity and specificity 72.1% and 86.1%, respectively, for galectin-3 and 69.8% and 58.1% for S100A9 in differentiating between PCDM and type 2 diabetes. CONCLUSIONS Galectin-3 and S100A9 are overexpressed in PCDM tumors and mediate insulin resistance. Galectin-3 and S100A9 distinguish PCDM from type 2 diabetes in subjects with new-onset diabetes. ? 2019 by the American Diabetes Association.
SDGs
Other Subjects
calgranulin B; galectin 3; insulin; calgranulin B; galectin 3; galectin-3, human; tumor marker; Article; bioinformatics; C2C12 cell line; cancer patient; controlled study; diabetic patient; disease association; disease classification; female; glucose transport; human; human cell; human tissue; immunohistochemistry; insulin resistance; major clinical study; male; MIA PaCa-2 cell line; myotube; non insulin dependent diabetes mellitus; pancreas cancer; protein blood level; protein expression; proteomics; sensitivity and specificity; transcriptomics; adult; blood; complication; differential diagnosis; gene expression profiling; genetics; middle aged; non insulin dependent diabetes mellitus; pancreas tumor; Adult; Biomarkers, Tumor; Calgranulin B; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Galectin 3; Gene Expression Profiling; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Pancreatic Neoplasms; Proteomics; Sensitivity and Specificity
Publisher
American Diabetes Association Inc.
Type
journal article