Evidence map›Paper›PMID 41220933›Full record

ArticleFrontiers in oncology2025

Genetically instrumented circulating metabolites and hepatobiliary cancer risk: A multi-tiered Mendelian randomization and functional interrogation.

Lin Tuo, Li Ting Yan, Ying Liu, Shu Qiang Wang, Xing Xiang Yang, Xiang An

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Article in Frontiers in oncology, 2025. 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

What it found

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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

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3 · Its place in the literature

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No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Lin TuoDepartment of Infectious Disease, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Li Ting YanDepartment of Infectious Disease, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Ying LiuDepartment of Infectious Disease, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Shu Qiang WangDepartment of Infectious Disease, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Xing Xiang YangDepartment of Infectious Disease, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Xiang AnDepartment of Hepatobiliary and Pancreatic Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Hepatobiliary malignancies-including hepatocellular carcinoma and cholangiocarcinoma-are major causes of cancer-related mortality worldwide, yet their regulatory pathways remain incompletely defined. Methods: We employed a two-sample Mendelian randomization (MR) approach to systematically investigate causal relationships between 1,400 serum metabolites and hepatobiliary cancer risk. Through stringent quality control (all SNPs with F-statistics > 10) and sensitivity analyses (MR-Egger regression, weighted median method, and MR-PRESSO), we identified 10 candidate metabolites. Results: Meta-analysis confirmed three metabolites with robust associations: risk-increasing dimethylarginine (SDMA+ADMA) and 4-hydroxyhippurate, and protective 3-hydroxyisobutyrate. Multivariable MR validated the independent effects of 4-hydroxyhippurate and 3-hydroxyisobutyrate. In vitro functional experiments demonstrated that 4-hydroxyhippurate promoted, whereas 3-hydroxyisobutyrate inhibited, hepatocellular carcinoma cell proliferation. Conclusion: These findings advance understanding of metabolic dysregulation in hepatobiliary malignancies and nominate candidate diagnostic biomarkers and therapeutic targets, providing translationally relevant hypotheses for precision medicine.

Indexed as

3-hydroxyisobutyrate4-hydroxyhippuratecirculating metaboliteshepatobiliary malignanciesmultivariable mendelian randomization analysis

Identifiers

PMID41220933
PMCPMC12597744

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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 Socratic graph.