MUC17是一种潜在的新预后生物标志物，可促进梗阻性黄疸中胰腺癌的进展。

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

作者信息

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

机构信息

Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.

Regenerative Medicine and Cellular Pharmacology Research Laboratory, Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.

出版信息

Oncology. 2025;103(8):725-741. doi: 10.1159/000541874. Epub 2024 Oct 11.

DOI:10.1159/000541874

PMID:39396510

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12324704/

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.

摘要

引言

我们的研究小组之前已经表明，胆汁酸（BAs）会加速胰腺癌（PC）的致癌过程，其中黏蛋白4（MUC4）的表达起着核心作用。然而，其他黏蛋白在胰腺癌中的作用尚不清楚，尤其是在胆汁诱导的癌症进展中。本研究的目的是调查MUC17在经胆汁酸或人血清处理的胰腺导管腺癌（PDAC）细胞系中的表达情况。

方法

采用不同的基于细胞的RNA沉默/过表达实验来研究MUC17在癌症进展中的作用。通过免疫组织化学评估55例人类胰腺样本中MUC17的蛋白表达，并使用Kaplan-Meier生存分析比较生存曲线。

结果

MUC17在PDAC患者中的表达增加，尤其是在梗阻性黄疸（OJ）患者中，MUC17表达升高与较差的总生存率相关（10.66±1.99个月 vs. 15.05±2.03个月；对数秩检验：0.0497）。用胆汁酸或从PDAC + OJ患者获得的人血清处理Capan-1和AsPC-1细胞，可增强MUC17的表达以及细胞的增殖潜能，而单独敲低MUC17或与MUC4联合敲低可降低胆汁酸诱导的致癌过程。