In this initial validation study, the biomarkers glypican-1 and CD63 were found to reflect the presence of PDAC and thus were used to develop a bivariate model for detecting PDAC.
However, GPC1 levels were enriched in PDAC crExos (<i>n</i> = 11), compared to the source tumors (<i>n</i> = 11; 97 ± 54 vs. 20.9 ± 12.3 pg/mL; <i>P</i> < 0.001).
Receiver operating characteristic curve (ROC) analysis showed that serum CA19-9 was significantly better than serum GPC1 in distinguishing PDAC patients from the controls (AUC, 95% CI: 0.908, 0.868-0.947 vs 0.795, 0.749-0.841, respectively).
An aberrant overexpression of GPC1 protein which is usually absent in normal pancreatic duct, was a widespread marker across the full spectrum of human PDAC precursors, PDAC, and pancreatic cancerous stroma.
We demonstrated that GPC1 mRNA was silenced in normal pancreata; however, it was re-expressed in PDAC tissues probably because of the promoter hypomethylation.
Thus, our exosomal miR signature is superior to exosomal GPC1 or plasma CA 19-9 levels in establishing a diagnosis of PDAC and differentiating between PDAC and CP.
QRT-PCR demonstrated increased GPC1 mRNA levels in pancreatic ductal adenocarcinoma (PDAC) compared to normal pancreatic tissues (NPT), as described previously.