Evidence map›Paper›PMID 42033493›Full record

ArticleCellular and molecular life sciences : CMLS2026

The bile acid TUDCA promotes chemoresistance and predicts survival through MAPK signaling in pancreatic ductal adenocarcinoma.

Yanling Wang, Shengbai Xue, Haiyan Xu, Jingyu Ma, Siming Wu, Keying Guo, Yaqun Fang, Jiujie Cui, Liwei Wang

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Yanling Wang *Department of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Pudong District, Shanghai, China.
Shengbai Xue *Department of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Pudong District, Shanghai, China.
Haiyan XuDepartment of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Pudong District, Shanghai, China.
Jingyu MaDepartment of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Pudong District, Shanghai, China.
Siming WuDepartment of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Pudong District, Shanghai, China.
Keying GuoDepartment of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Pudong District, Shanghai, China.
Yaqun FangDepartment of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Pudong District, Shanghai, China.
Jiujie CuiDepartment of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Pudong District, Shanghai, China. cuijiujie@126.com.
Liwei WangDepartment of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Pudong District, Shanghai, China. liweiwang@shsmu.edu.cn.ORCID http://orcid.org/0000-0002-4122-4444

Funding

National Natural Science Foundation of China 82103087National Natural Science Foundation of China 82171824National Natural Science Foundation of China 82272906National Natural Science Foundation of China 82373133Project from CSCO Clinical Oncology Research Foundation Y-2019AZZD-0513Science and Technology Commission of Shanghai Municipality 25SF1900600Science and Technology Commission of Shanghai Municipality 25ZR1402469Shanghai Leading Talents Project, and the Innovative Research Team of High-Level Local Universities in Shanghai SHSMU-ZDCX20210802Shanghai Municipal Education Commission - Gao Feng Clinical Medicine Grant Support 20161312
6 · The paper itself

Abstract

Our study comprehensively investigated the prognostic significance and biological mechanisms of bile acids in patients with advanced pancreatic adenocarcinoma (PC) through clinical data analysis, in vitro cell assays, and in vivo xenograft models. A total of 101 patients with advanced pancreatic adenocarcinoma were followed up in this study. Multivariate Cox regression identified elevated total bile acids (tBA) as an independent risk factor for progression-free survival (PFS). Patients with high tBA exhibited significantly shorter PFS and overall survival (OS), alongside impaired liver function and an immunosuppressive profile. Bile acid mass spectrometry further identified tauro-ursodeoxycholic acid (TUDCA) as a key subtype strongly associated with poor survival and a diminished response to first-line gemcitabine-based chemotherapy. ROC analysis confirmed that TUDCA outperformed tBA and other clinical indicators in predicting treatment outcomes. Mechanistically, TUDCA did not affect pancreatic cancer cell proliferation but significantly attenuated gemcitabine-induced cytotoxicity both in vitro and in vivo by inhibiting apoptosis. RNA sequencing and western blot analyses revealed that TUDCA confers chemoresistance by activating the MAPK signaling pathway. Notably, the MEK1/2 inhibitor trametinib successfully reversed TUDCA-mediated resistance in experimental models. These findings identify TUDCA as a novel prognostic biomarker and a potential therapeutic target to enhance chemotherapy efficacy in advanced PC.

Indexed as

Carcinoma, Pancreatic DuctalDrug Resistance, NeoplasmMAP Kinase Signaling SystemPancreatic NeoplasmsTaurochenodeoxycholic AcidAgedAnimalsApoptosisCell Line, TumorCell ProliferationDeoxycytidineFemaleGemcitabineHumansMaleMiceDeoxycytidineGemcitabineTaurochenodeoxycholic AcidursodoxicoltaurineBile acidGemcitabine resistancePancreatic ductal adenocarcinomaPrognostic biomarkersTUDCA

Identifiers

PMID42033493
PMCPMC13247006

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Registered trials

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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.