Evidence map›Paper›PMID 41408647›Full record

ArticleBiomarker research2025

Glycochenodeoxycholic acid promotes hepatocarcinogenesis by inducing hepatic progenitor cell differentiation into cancer-associated fibroblasts via sphingosine-1-phosphate receptor 2 signalling.

Lu Gao, Gang Lv, Ying Huang, Mengmeng Xue, Zhipeng Zhang, Jing Weng, Haoran Bai, Min Tao, Xi Luo, Yuhua Gao and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomarker research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Lu Gao *Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
Gang Lv *Senior Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Ying Huang *State Key Laboratory of Female Fertility Promotion, Department of Endocrinology and Metabolism, Third Hospital, Peking University, Beijing, China.
Mengmeng Xue *School of Pharmacy, Anhui Medical University, Hefei, China.
Zhipeng ZhangDepartment of General Surgery, Peking University Third Hospital, Peking University, Beijing, China.
Jing WengDepartment of General Surgery, Peking University Third Hospital, Peking University, Beijing, China.
Haoran BaiDepartment of Oncology, Longhua Hospital Affiliated to , Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Min TaoSchool of Pharmacy, Anhui Medical University, Hefei, China.
Xi LuoDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
Yuhua GaoDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
Shiyao FengDepartment of Urology, Chao hu Hospital of Anhui Medical University, Anhui, China.
Xiaojuan HouDepartment of Tumor Immune and Metabolism, National Center for Liver Cancer, Naval Medical University, Shanghai, China.
Chen ZongDepartment of Tumor Immune and Metabolism, National Center for Liver Cancer, Naval Medical University, Shanghai, China.
Xue YangDepartment of Tumor Immune and Metabolism, National Center for Liver Cancer, Naval Medical University, Shanghai, China.
Qiudong ZhaoDepartment of Tumor Immune and Metabolism, National Center for Liver Cancer, Naval Medical University, Shanghai, China.
Jinghua JiangDepartment of Tumor Immune and Metabolism, National Center for Liver Cancer, Naval Medical University, Shanghai, China.
Xinyu ZhuChanghai Clinical Research Unit, Changhai Hospital of Naval Medical University, Shanghai, China.
Zhipeng HanDepartment of Oncology, Longhua Hospital Affiliated to , Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Changtao JiangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
Dongyu ZhaoDepartment of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing, China. zhaodongyu@bjmu.edu.cn.
Lixin WeiDepartment of Tumor Immune and Metabolism, National Center for Liver Cancer, Naval Medical University, Shanghai, China. lixinwei@smmu.edu.cn.
Lulu SunState Key Laboratory of Female Fertility Promotion, Department of Endocrinology and Metabolism, Third Hospital, Peking University, Beijing, China. lulusun@bjmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients with advanced hepatocellular carcinoma (HCC) often develop cholestasis and exhibit poor clinical outcomes. Current evidence suggests that dysregulated bile acid metabolism may contribute to HCC progression, although the underlying molecular mechanisms remain unclear. Among the bile acids, glycochenodeoxycholic acid (GCDCA) is a key component of cholestasis. Under pathological conditions, hepatic progenitor cells (HPCs) transform into fibroblasts or tumor-initiating cells, directly promoting liver fibrosis and HCC development. This study aimed to investigate the regulatory role of GCDCA in the activation and differentiation of HPCs to elucidate its potential mechanisms in hepatocarcinogenesis.

methodsSingle-cell RNA sequencing was used to infer the heterogeneity of cancer-associated fibroblasts (CAFs) and their differentiation relationship with HPCs in a diethylnitrosamine-induced rat model. The TCGA and GEO datasets were used to assess the prognostic value of inflammatory CAFs (iCAFs) in patients with HCC. Transcriptomic sequencing, functional assays, and in vivo experiments were performed to validate the role of GCDCA in HCC pathogenesis.

resultsWe identified a CAF subset closely associated with the development of HCC (PDGFRA+CAFs). GCDCA promotes the differentiation of HPCs into PDGFRA+CAFs, which is mediated by sphingosine-1-phosphate receptor 2 (S1PR2). Treatment with the S1PR2 inhibitor JTE-013 markedly inhibited the progression of the pro-fibrotic phenotype in HPCs, which consequently reduced tumor growth and fibrosis in rats.

conclusionsGCDCA-induced differentiation of HPCs into PDGFRA+CAFs plays a critical role in HCC progression, driven by the S1PR2 receptor. These results provide new insights into the mechanisms underlying HPCs-mediated hepatocarcinogenesis. Targeting S1PR2 represents a promising therapeutic strategy for HCC with potential benefits in reducing fibrosis and tumorigenesis.

Indexed as

Cancer-associated fibroblastsGlycochenodeoxycholic acidHepatic progenitor cellsHepatocellular carcinomaSphingosine-1-phosphate receptor 2

Identifiers

PMID41408647
PMCPMC12709717

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.