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in the Liver–Gut Axis throughout the Whole Inflammation-Cancer Transformation Progressive: Reveal Hepatocellular Carcinoma Pathogenesis  \nLuwen Xing†, Yiwen Zhang†, Saiyu Li, Minghui Tong, Kaishun Bi, Qian Zhang * and Qing Li *  \nCitation: 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  \nAcademic Editor: Nam Deuk Kim  \nReceived: 13 January 2023  \nRevised: 4 February 2023  \nAccepted: 6 February 2023  \nPublished: 21 February 2023  \nCopyright: © 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/)) .  \nFaculty of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China  \n* 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.  \nAbstract: 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.  \nKeywords: hepatocellular carcinoma; inflammation-cancer transformation process; bile acids; enterohepatic circulation; BAAT; liver–gut axis  \n1. Introduction  \nHCC 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","cbCaignDfEzp8I93","https://ap.wps.com/l/cbCaignDfEzp8I93","pdf",4240452,16,"English","# Introduction\n# Materials and Methods\n# Results\n## Bile acid profiling across plasma, liver, and intestine\n## Biomarkers for early HCC diagnosis\n## BAAT identification via gene set enrichment analysis\n# Discussion and Conclusion","[{\"question\":\"What disease progression model was used to study HCC development?\",\"answer\":\"The research reproduced HCC development using an N-nitrosodiethylamine (DEN)-induced rat model over 20 weeks, tracking the transition across “hepatitis-cirrhosis-HCC.”\"},{\"question\":\"How were bile acids quantified across different organs in the study?\",\"answer\":\"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.\"},{\"question\":\"Which bile acid biomarkers were identified for early HCC diagnosis?\",\"answer\":\"The study identified chenodeoxycholic acid, lithocholic acid, ursodeoxycholic acid, and glycolithocholic acid in plasma as biomarkers for early diagnosis of HCC.\"}]","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 | PDF",1790220082]