A Dual Coverage Monitoring of the Bile Acids Profile in the Liver–Gut Axis throughout the Whole Inﬂammation-Cancer Transformation Progressive - Reveal Hepatocellular Carcinoma Pathogenesis

Sep 24, 2026

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Hepatocellular carcinoma (HCC) represents the terminal stage of multiple chronic liver diseases, with chronic uncontrolled inflammation implicated as a key driver. Dysregulated bile acid homeostasis within the enterohepatic circulation is a major research focus for clarifying inflammation-to-cancer pathogenesis. Using a DEN-induced rat model, the study monitored bile acid profiles across plasma, liver, and intestine during “hepatitis-cirrhosis-HCC,” applying ultra-performance liquid chromatography-tandem mass spectrometry for absolute quantification.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Materials and Methods

Results

Bile acid profiling across plasma, liver, and intestine

Biomarkers for early HCC diagnosis

BAAT identification via gene set enrichment analysis

Discussion and Conclusion

Article A Dual Coverage Monitoring of the Bile Acids Proﬁle in the Liver–Gut Axis throughout the Whole Inﬂammation-Cancer Transformation Progressive: Reveal Hepatocellular Carcinoma Pathogenesis Luwen Xing†, Yiwen Zhang†, Saiyu Li, Minghui Tong, Kaishun Bi, Qian Zhang * and Qing Li * Citation: Xing, L.; Zhang, Y.; Li, S.; Tong, M.; Bi, K.; Zhang, Q.; Li, Q. A Dual Coverage Monitoring of the Bile Acids Proﬁle in the Liver–Gut Axis throughout the Whole InﬂammationCancer Transformation Progressive: Reveal Hepatocellular Carcinoma Pathogenesis. Int. J. Mol. Sci. 2023, 24, 4258. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24054258 Academic Editor: Nam Deuk Kim Received: 13 January 2023 Revised: 4 February 2023 Accepted: 6 February 2023 Published: 21 February 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/)) . Faculty of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China * Correspondence: [zhangqian@syphu.edu.cn](zhangqian@syphu.edu.cn) (Q.Z.); [101040108@syphu.edu.cn](101040108@syphu.edu.cn) (Q.L.)† These authors contributed equally to this work. Abstract: Hepatocellular carcinoma (HCC) is the terminal phase of multiple chronic liver diseases, and evidence supports chronic uncontrollable inﬂammation being one of the potential mechanisms leading to HCC formation. The dysregulation of bile acid homeostasis in the enterohepatic circulation has become a hot research issue concerning revealing the pathogenesis of the inﬂammatory-cancerous transformation process. We reproduced the development of HCC through an N-nitrosodiethylamine (DEN)-induced rat model in 20 weeks. We achieved the monitoring of the bile acid proﬁle in the plasma, liver, and intestine during the evolution of “hepatitis-cirrhosis-HCC” by using an ultra-performance liquid chromatography-tandem mass spectrometer for absolute quantiﬁcation of bile acids. We observed differences in the level of primary and secondary bile acids both in plasma, liver, and intestine when compared to controls, particularly a sustained reduction of intestine taurine-conjugated bile acid level. Moreover, we identiﬁed chenodeoxycholic acid, lithocholic acid, ursodeoxycholic acid, and glycolithocholic acid in plasma as biomarkers for early diagnosis of HCC. We also identiﬁed bile acid-CoA:amino acid N-acyltransferase (BAAT) by gene set enrichment analysis, which dominates the ﬁnal step in the synthesis of conjugated bile acids associated with the inﬂammatory-cancer transformation process. In conclusion, our study provided comprehensive bile acid metabolic ﬁngerprinting in the liver–gut axis during the inﬂammation-cancer transformation process, laying the foundation for providing a new perspective for the diagnosis, prevention, and treatment of HCC. Keywords: hepatocellular carcinoma; inﬂammation-cancer transformation process; bile acids; enterohepatic circulation; BAAT; liver–gut axis 1. Introduction HCC is one of the most serious malignancy tumors threatening human health, the third leading cause of cancer-related death in the world [1–3] . Persistent inﬂammation leading to the formation of the tumor microenvironment is an important factor in the formation of HCC, whose mechanism is very complicated. The morbidity trend of HCC appears to be closely related to hepatitis B (HBV) infection, and it has been reported that HCC patients caused by HBV still account for more than half of the global cases [4–6] . Although the inﬂammation-cancer transformation process of “hepatitis-cirrhosis-HCC”has become a research highlight to reveal the pathogenesis of HCC, there is still no effective clinical t

FAQs

What disease progression model was used to study HCC development?

The research reproduced HCC development using an N-nitrosodiethylamine (DEN)-induced rat model over 20 weeks, tracking the transition across “hepatitis-cirrhosis-HCC.”

How were bile acids quantified across different organs in the study?

Bile acid profiles in plasma, liver, and intestine were monitored using an ultra-performance liquid chromatography-tandem mass spectrometer for absolute quantification, based on bile-acid profiling methods described in the abstract.

Which bile acid biomarkers were identified for early HCC diagnosis?

The study identified chenodeoxycholic acid, lithocholic acid, ursodeoxycholic acid, and glycolithocholic acid in plasma as biomarkers for early diagnosis of HCC.

Sep 24, 2026

Uploaded by Jiven