MUC17 Is a Potential New Prognostic Biomarker and Promotes Pancreatic Cancer Progression in Obstructive Jaundice

Our working group has previously shown that bile acids (BAs) accelerate carcinogenic processes in pancreatic cancer (PC) in which mucin 4 (MUC4) expression has a central role. However, the role of other mucins in PC is less clear, especially in bile-induced cancer progression. The study aim was to investigate expression of MUC17 in BA- or human serum-treated pancreatic ductal adenocarcinoma (PDAC) cell lines.

Different cell-based assays with RNA silencing/overexpression were used to study the role of MUC17 in cancer progression. Protein expression of MUC17 was evaluated in 55 human pancreatic samples by immunohistochemistry, and Kaplan-Meier survival analysis was used to compare survival curves.

Expression of MUC17 increased in PDAC patients, especially in obstructive jaundice (OJ), and the elevated MUC17 expression associated with poorer overall survival (10.66 ± 1.99 vs. 15.05 ± 2.03 months; log-rank: 0.0497). Treatment of Capan-1 and AsPC-1 cells with BAs or with human serum obtained from PDAC + OJ patients enhanced the expression of MUC17, as well as the proliferative potential of the cells, whereas knockdown of MUC17 alone or in combination with MUC4 decreased BAs-induced carcinogenic processes.

Our results demonstrated that MUC17 has a central role in bile-induced PC progression, and in addition to MUC4, this isoform also can be used as a novel prognostic biomarker.