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Hypoxia-Induced TGFBI as a Serum Biomarker for Laboratory Diagnosis and Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

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-β-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.