ABSTRACT
OBJECTIVE: To explore novel biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC), from the perspective of tumor hypoxia. METHODS: We screened 29 differentially expressed and hypoxia-upregulated genes from the Oncomine database. A total of 12 secretory proteins that interact with hypoxia-inducible factor 1 (HIF-1A) were selected by STRING (protein-protein interaction networks). After excluding enzymes and collagens, insulin-like growth factor-binding protein 3 (IGFBP3), glycoprotein NBM (GPNMB), transforming growth factor-ß-induced (TGFBI), and biglycan (BGN) were detected by sandwich enzyme-linked immunosorbent assay (ELISA) in patients with cancer and healthy control individuals. RESULTS: The serum level of TGFBI was significantly elevated in patients with PDAC, compared with healthy controls; the assay could discriminate among cases of PDAC in different clinical stages. The amount of TGFBI was significantly decreased after treatment. The combination of TGFBI and cancer antigen (CA) 19-9 was more accurate than TGFBI or CA 19-9 alone as diagnostic markers. Also, TGFBI might be used as a prognostic marker according to the PROGgeneV2 Pan Cancer Prognostics Database. CONCLUSIONS: Serum TGFBI, combined with CA 19-9, offers higher diagnostic value than other methods for patients with PDAC. Also, TGFBI might be used as a prognostic marker.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Pancreatic Ductal/blood , Extracellular Matrix Proteins/blood , Pancreatic Neoplasms/blood , Transforming Growth Factor beta/blood , Biomarkers, Tumor/standards , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology , Extracellular Matrix Proteins/standards , Humans , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Transforming Growth Factor beta/standards , Tumor HypoxiaABSTRACT
The urinary transforming growth factor beta (TGF-beta) excretion was measured in 33 patients including 10 with systemic lupus erythematosus (SLE), 8 with focal glomerular sclerosis (FGS), 9 with IgA nephropathy (IgAN), and 6 with membranous nephropathy (MN), and in 7 healthy subjects by enzyme-linked immunosorbent assay using a monoclonal antibody specific for TGF-beta 1 + 2 + 3. A significantly increased urinary TGF-beta excretion was observed in FGS patients (555.5 +/- 458.4 ng/mg Cr) as compared with normal controls (46.9 +/- 43.9 ng/mg Cr) (p < 0.05) and a relative increase in SLE patients (96.4 +/- 58.2 ng/mg Cr) and a decrease in MN patients (24.8 +/- 13.3 ng/mg Cr). In contrast, there was no difference in TGF-beta excretion between IgAN patients (54.1 +/- 37.4 ng/mg Cr) and normal controls. A correlation between the amount of proteinuria and TGF-beta was not found. As has been previously demonstrated in experimental studies, TGF-beta may play a similar role in human glomerular diseases. The results obtained in this study raised the possibility that extracellular matrix might be produced by glomerular cells in vivo under the control of TGF-beta and that TGF-beta might act as a stimulator for the development of glomerulosclerosis.
