Understanding the Clinical Significance of MUC5AC in Biliary Tract Cancers

Sep 24, 2026

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Biliary tract cancers (BTC) arise from biliary epithelium and include cholangiocarcinomas (intrahepatic and extrahepatic) and gallbladder cancers. Limited treatment options, late presentation, recurrence, and poor systemic therapy response drive poor outcomes. MUC5AC is rarely expressed in normal biliary epithelium but can be upregulated in benign biliary disease, premalignant conditions, and BTC, with tissue expression varying widely by cancer subtype and methods. MUC5AC can be detected in BTC patients’ serum at high concentrations, yet diagnostic and prognostic value evidence remains inconsistent, requiring further studies.

LanguageEnglish

CategoryHealthcare

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Pages27

Reading Time1 h 8 min

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cancers Review Understanding the Clinical Signiﬁcance of MUC5AC in Biliary Tract Cancers Katherine K. Benson 1, Ankur Sheel 1, Shaﬁa Rahman 2, Ashwini Esnakula 3 and Ashish Manne 2, * Citation: Benson, K.K.; Sheel, A.; Rahman, S.; Esnakula, A.; Manne, A. Understanding the Clinical Signiﬁcance of MUC5AC in Biliary Tract Cancers. Cancers 2023, 15, 433 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers15020433 Received: 19 December 2022 Revised: 30 December 2022 Accepted: 4 January 2023 Published: 9 January 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH 43210, USA 2 Department of Internal Medicine, Division of Medical Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA 3 Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA * Correspondence: [ashish.manne@osumc.edu](ashish.manne@osumc.edu); Tel.: +1-614-366-2982 Simple Summary: Biliary tract cancers (BTC) are tumors arising from cells lining ducts in the liver that facilitate the transport of bile into the gastrointestinal tract. They are often divided into two broad groups, cholangiocarcinoma and gallbladder cancers. They are aggressive tumors with limited treatment options that are often ineffective and have bad outcomes. In current clinical practice, there are no good tests to identify these cancers in early stages and predict their aggressiveness or response to the available treatments. We shed light on the role of a glycoprotein, MUC5AC, in BTC including its potential impact on biliary cancer development. We discuss the clinical evidence surrounding the use of MUC5AC when detected in BTC patients' tumor tissue and blood and its potential use in managing these cancers. Abstract: Biliary tract cancers (BTC) arise from biliary epithelium and include cholangiocarcinomas or CCA (including intrahepatic (ICC) and extrahepatic (ECC)) and gallbladder cancers (GBC). They often have poor outcomes owing to limited treatment options, advanced presentations, frequent recurrence, and poor response to available systemic therapy. Mucin 5AC (MUC5AC) is rarely expressed in normal biliary epithelium, but can be upregulated in tissues of benign biliary disease, premalignant conditions (e.g., biliary intraepithelial neoplasia), and BTCs. This mucin's numerous glycoforms can be divided into less-glycosylated immature and heavily-glycosylated mature forms. Reported MUC5AC tissue expression in BTC varies widely, with some associations based on cancer location (e.g., perihilar vs. peripheral ICC) . Study methods were variable regarding cancer subtypes, expression positivity thresholds, and MUC5AC glycoforms. MUC5AC can be detected in serum of BTC patients at high concentrations. The hesitancy in developing MUC5AC into a clinically useful biomarker in BTC management is due to variable evidence on the diagnostic and prognostic value. Concrete conclusions on tissue MUC5AC are difﬁcult, but serum detection might be relevant for diagnosis and is associated with poor prognosis. Future studies are needed to further the understanding of the potential clinical value of MUC5AC in BTC, especially regarding predictive and therapeutic value. Keywords: biliary tract cancer; cholangiocarcinoma; gallbladder carcinoma; Mucin 5AC; MUC5AC; prognosis; diagnosis; biliary carcinogenesis; intrahepatic; extrahepatic 1. Introduction Biliary tract cancers (BTC) are tumors arising from the

FAQs

What are biliary tract cancers and why do they have poor outcomes?

Biliary tract cancers arise from biliary epithelium and include cholangiocarcinoma and gallbladder cancer. They often have poor outcomes due to limited treatment options, advanced presentation, frequent recurrence, and poor response to available systemic therapy.

What is MUC5AC and where is it expressed in relation to BTC?

MUC5AC is rarely expressed in normal biliary epithelium, but it can be upregulated in benign biliary disease, premalignant conditions, and biliary tract cancers.

How is MUC5AC evaluated for clinical use, and what limits its use as a biomarker?

MUC5AC is assessed in tumor tissue and can also be detected in serum at high concentrations. Development into a clinically useful biomarker is limited by variable evidence regarding its diagnostic and prognostic value, including inconsistent tissue findings and variable study methods.

Sep 24, 2026

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