rBC2LCN-reactive SERPINA3 is a glycobiomarker candidate for pancreatic ductal adenocarcinoma.

Early detection is urgently needed to improve the patient's pancreatic ductal adenocarcinoma (PDAC) survival. Previously, we identified a novel tumor-associated glycan, H-type3, which is expressed on PDAC cells and is detected by rBC2LCN lectin. Here, we identified that SERPINA3 is an rBC2LCN-reactive glycoprotein (BC2-S3) secreted from PDAC cells into the blood in patients with PDAC by LC-MS/MS analysis and lectin blotting. In immune staining, BC2-S3 was detected specifically in the tumor, but not in normal tissues of PDAC. Lectin-ELISA was then developed to measure the serum level of BC2-S3 in healthy control (HC, n = 99) and patients with PDAC (n = 88). BC2-S3 exhibited higher in patients with PDAC than in those with HC. BC2-S3 showed similar diagnostic performance in all stages of PDAC (stage IA-IV, true positive rate 76.1 percent, true negative rate 81.8 percent) to CA19-9 (72.7 percent, 75.8 percent). Remarkably, BC2-S3 showed a significantly higher detection rate (89.7 percent) for early-stage PDAC (IA-IIA) than CA19-9 (62.1 percent, P = 0.029). The combination of BC2-S3 and CA19-9 further improved the diagnostic ability for all stages of PDAC (81.8 percent, 87.9 percent). In conclusion, BC2-S3 is a glycobiomarker candidate for PDAC.