Evidence map›Paper›PMID 41694488›Full record

ArticleWorld journal of gastroenterology2026

Lactate metabolism-driven tumor heterogeneity and molecular signatures in intrahepatic cholangiocarcinoma.

An-Ke Wu, Jun-Yi Li, Kai Zhang, Martin Meng, Xue Wang, Yue Liu, Peng Xie, Wei-Qi Rong, Fan Wu, Hong-Guang Wang and 2 more

Abstract read
In one paragraph

Article in World journal of gastroenterology, 2026. 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

12 authors.

An-Ke WuDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Jun-Yi LiState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Kai ZhangDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Martin MengDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, United States.
Xue WangDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, United States.
Yue LiuDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Peng XieDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Wei-Qi RongDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Fan WuDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Hong-Guang WangDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Xuan MengDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Jian-Xiong WuDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. dr_wujx@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntrahepatic cholangiocarcinoma (ICC) is a highly aggressive liver malignancy with limited therapeutic options and poor prognosis. Recent evidence indicates that lactate metabolism (LM) plays a pivotal role in tumor metabolic reprogramming, immune evasion, and disease progression; however, the heterogeneity and regulatory mechanisms of LM activity within ICC remain largely undefined.

aimTo systematically characterize LM-driven heterogeneity and its molecular and functional implications in ICC.

methodsSingle-cell RNA sequencing and bulk transcriptomic datasets were integrated to characterize LM heterogeneity in ICC. High-dimensional weighted gene co-expression network analysis and multiple machine-learning algorithms (least absolute shrinkage and selection operator, random forest, gradient boosting machine, adaptive best subset selection, and decision tree) were employed to identify LM-associated feature genes. CytoTRACE and CellChat analyses were used to assess differentiation potential and intercellular communication among malignant epithelial subpopulations. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed to elucidate biological functions. A random forest model combined with SHapley Additive exPlanation (SHAP) interpretability analysis identified the most predictive LM-related gene. Functional assays, including quantitative polymerase chain reaction, cell counting kit-8, colony formation, wound-healing, and transwell experiments, were conducted to validate

resultsMalignant ICC cells were stratified into three LM-activity subtypes (high, intermediate, and low) exhibiting distinct transcriptional programs and differentiation trajectories. Twelve LM-associated feature genes

conclusionThis integrative single-cell and machine-learning study delineates the molecular heterogeneity of LM in ICC and identifies twelve feature genes linking LM with tumor aggressiveness. These findings provide novel insight into LM-driven oncogenic mechanisms and propose

Indexed as

Bile Duct NeoplasmsBiomarkers, TumorCholangiocarcinomaLactic AcidCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansMachine LearningMetabolic ReprogrammingPrognosisSingle-Cell Gene Expression AnalysisTranscriptomeBiomarkers, TumorLactic AcidIntrahepatic cholangiocarcinomaLactate metabolismMetabolic heterogeneitySingle-cell RNA sequencingTumor microenvironment

Identifiers

PMID41694488
PMCPMC12897937

What OpenQuestion holds

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LicenceCC BY-NC
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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.