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

Eleonóra Gál; István Menyhárt; Zoltán Veréb; Lajos Kemény; László Tiszlavicz; Zoltán Márton Köhler; Anikó Keller-Pintér; Dávid Rakk; András Szekeres; Tamás Takács; László Czakó; Péter Hegyi; Boshra Yosef; Viktória Venglovecz

doi:10.1159/000541874

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

Oncology. 2024 Oct 11:1-17. doi: 10.1159/000541874. Online ahead of print.

Authors

Eleonóra Gál¹, István Menyhárt¹, Zoltán Veréb^{2

3}, Lajos Kemény^{2

3}, László Tiszlavicz⁴, Zoltán Márton Köhler⁵, Anikó Keller-Pintér⁵, Dávid Rakk⁶, András Szekeres⁶, Tamás Takács⁷, László Czakó⁷, Péter Hegyi^{8

9

10

11}, Boshra Yosef¹, Viktória Venglovecz^{1

8

11}

Affiliations

¹ Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
² Regenerative Medicine and Cellular Pharmacology Research Laboratory, Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
³ HCEMM SZTE Skin Research Group, University of Szeged, Szeged, Hungary.
⁴ Department of Pathology, University of Szeged, Szeged, Hungary.
⁵ Department of Biochemistry, University of Szeged, Szeged, Hungary.
⁶ Department of Microbiology, University of Szeged, Szeged, Hungary.
⁷ Department of Medicine, University of Szeged, Szeged, Hungary.
⁸ Translational Pancreatology Research Group, Interdisciplinary Center of Excellence for Research Development and Innovation, University of Szeged, Szeged, Hungary.
⁹ Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
¹⁰ Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
¹¹ Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.

PMID: 39396510
DOI: 10.1159/000541874

Abstract

Introduction: 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.

Keywords: Bile acids; MUC17; MUC4; Obstructive jaundice; Pancreatic cancer.