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

• Published in: Oncology Vol. 103; no. 8; pp. 725 - 741
• Main Authors: Gál, Eleonóra, Menyhárt, István, Veréb, Zoltán, Kemény, Lajos, Tiszlavicz, László, Köhler, Zoltán Márton, Keller-Pintér, Anikó, Rakk, Dávid, Szekeres, András, Takács, Tamás, Czakó, László, Hegyi, Péter, Yosef, Boshra, Venglovecz, Viktória
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01.08.2025
• Subjects: Aged; Bile Acids and Salts - pharmacology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Cell Line, Tumor; Cell Proliferation; Clinical Translational Research; Disease Progression; Female; Humans; Jaundice, Obstructive - metabolism; Jaundice, Obstructive - pathology; Male; Middle Aged; Mucin-4 - genetics; Mucin-4 - metabolism; Mucins - genetics; Mucins - metabolism; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Prognosis; Obstructive jaundice; Bile acids; MUC17; MUC4; Pancreatic cancer
• ISSN: 0030-2414; 1423-0232
• DOI: 10.1159/000541874

AbstractIntroduction: 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. Methods: 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. Results: 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. Conclusion: 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.