Dysregulation of bile acid metabolism in patients with colorectal cancer

Abstract Bile acid (BA) metabolism and signaling may influence cancer risk. We investigated differences in circulating BA composition between healthy controls and patients with colorectal cancer (CRC) and assessed the epithelial–mesenchymal transition (EMT) in CRC cell lines exposed to chenodeoxycho...

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Main Authors: Su-Mi Lee, Seon-Young Park, Khom Sophallika, Jin Ook Chung, Yong Wook Jung, Dong Hyun Kim, Jin Won Kim, Hyun Soo Kim, Jae Hyun Yoon, Young Do Jung, Jae Kyun Ju, Jun Seong Chung, Han Deok Kwak
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Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-15159-6
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author Su-Mi Lee
Seon-Young Park
Khom Sophallika
Jin Ook Chung
Yong Wook Jung
Dong Hyun Kim
Jin Won Kim
Hyun Soo Kim
Jae Hyun Yoon
Young Do Jung
Jae Kyun Ju
Jun Seong Chung
Han Deok Kwak
author_facet Su-Mi Lee
Seon-Young Park
Khom Sophallika
Jin Ook Chung
Yong Wook Jung
Dong Hyun Kim
Jin Won Kim
Hyun Soo Kim
Jae Hyun Yoon
Young Do Jung
Jae Kyun Ju
Jun Seong Chung
Han Deok Kwak
author_sort Su-Mi Lee
collection DOAJ
description Abstract Bile acid (BA) metabolism and signaling may influence cancer risk. We investigated differences in circulating BA composition between healthy controls and patients with colorectal cancer (CRC) and assessed the epithelial–mesenchymal transition (EMT) in CRC cell lines exposed to chenodeoxycholic acid (CDCA). BA, C4, and fibroblast growth factor-19 (FGF19) concentrations in serum samples from 70 controls and 133 patients with CRC were analyzed. Results showed that primary and secondary BAs, C4, and FGF19 were significantly lower in CRC patients than in the age- and sex- matched controls (P < 0.05). CDCA reduced the percentage of EdU-positive cells in HCT116 and HT-29 cells by 53.6% and 28.3%, respectively (P < 0.001) and decreased the rate of wound closure by 0.31 ± 0.05- and 0.30 ± 0.06-fold in HCT116 and HT-29 cells, respectively(P < 0.05). It significantly reduced spheroid formation by 90.0% and 94.3% in HCT116 and HT-29 cells, respectively (P < 0.0001) and downregulated EMT-related stem cell markers in CRC cells. The dysregulation of BA synthesis and recycling might contribute to CRC carcinogenesis. CDCA might alter EMT, protecting against CRC development and progression. The predictive role of plasma BAs in CRC prognosis and their potential in CRC prevention and management should be further explored.
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spelling doaj-art-dcc4076fbbf240628a32ade148343b492025-08-20T03:42:38ZengNature PortfolioScientific Reports2045-23222025-08-0115111010.1038/s41598-025-15159-6Dysregulation of bile acid metabolism in patients with colorectal cancerSu-Mi Lee0Seon-Young Park1Khom Sophallika2Jin Ook Chung3Yong Wook Jung4Dong Hyun Kim5Jin Won Kim6Hyun Soo Kim7Jae Hyun Yoon8Young Do Jung9Jae Kyun Ju10Jun Seong Chung11Han Deok Kwak12Department of Internal Medicine, Chonnam National University Medical SchoolDepartment of Internal Medicine, Chonnam National University Medical SchoolDepartment of Internal Medicine, Chonnam National University Medical SchoolDepartment of Internal Medicine, Chonnam National University Medical SchoolDepartment of Internal Medicine, Chonnam National University Medical SchoolDepartment of Internal Medicine, Chonnam National University Medical SchoolDepartment of Internal Medicine, Chonnam National University Medical SchoolDepartment of Internal Medicine, Chonnam National University Medical SchoolDepartment of Internal Medicine, Chonnam National University Medical SchoolDepartment of Biochemistry, Chonnam National University Medical SchoolDepartment of General Surgery, Chonnam National University Medical SchoolDepartment of General Surgery, Chonnam National University Medical SchoolDepartment of General Surgery, Chonnam National University Medical SchoolAbstract Bile acid (BA) metabolism and signaling may influence cancer risk. We investigated differences in circulating BA composition between healthy controls and patients with colorectal cancer (CRC) and assessed the epithelial–mesenchymal transition (EMT) in CRC cell lines exposed to chenodeoxycholic acid (CDCA). BA, C4, and fibroblast growth factor-19 (FGF19) concentrations in serum samples from 70 controls and 133 patients with CRC were analyzed. Results showed that primary and secondary BAs, C4, and FGF19 were significantly lower in CRC patients than in the age- and sex- matched controls (P < 0.05). CDCA reduced the percentage of EdU-positive cells in HCT116 and HT-29 cells by 53.6% and 28.3%, respectively (P < 0.001) and decreased the rate of wound closure by 0.31 ± 0.05- and 0.30 ± 0.06-fold in HCT116 and HT-29 cells, respectively(P < 0.05). It significantly reduced spheroid formation by 90.0% and 94.3% in HCT116 and HT-29 cells, respectively (P < 0.0001) and downregulated EMT-related stem cell markers in CRC cells. The dysregulation of BA synthesis and recycling might contribute to CRC carcinogenesis. CDCA might alter EMT, protecting against CRC development and progression. The predictive role of plasma BAs in CRC prognosis and their potential in CRC prevention and management should be further explored.https://doi.org/10.1038/s41598-025-15159-6Bile acidsColorectal cancerEpithelial–mesenchymal transitionChenodeoxycholic acid
spellingShingle Su-Mi Lee
Seon-Young Park
Khom Sophallika
Jin Ook Chung
Yong Wook Jung
Dong Hyun Kim
Jin Won Kim
Hyun Soo Kim
Jae Hyun Yoon
Young Do Jung
Jae Kyun Ju
Jun Seong Chung
Han Deok Kwak
Dysregulation of bile acid metabolism in patients with colorectal cancer
Scientific Reports
Bile acids
Colorectal cancer
Epithelial–mesenchymal transition
Chenodeoxycholic acid
title Dysregulation of bile acid metabolism in patients with colorectal cancer
title_full Dysregulation of bile acid metabolism in patients with colorectal cancer
title_fullStr Dysregulation of bile acid metabolism in patients with colorectal cancer
title_full_unstemmed Dysregulation of bile acid metabolism in patients with colorectal cancer
title_short Dysregulation of bile acid metabolism in patients with colorectal cancer
title_sort dysregulation of bile acid metabolism in patients with colorectal cancer
topic Bile acids
Colorectal cancer
Epithelial–mesenchymal transition
Chenodeoxycholic acid
url https://doi.org/10.1038/s41598-025-15159-6
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