Evidence map›Paper›PMID 41299678›Full record

ArticleJournal of translational medicine2025

D-amino acid oxidase suppresses hepatocellular carcinoma via oxidizing D-amino acids.

Zishuai Li, Chao Fu, Yifan Chen, Letian Fang, Wenbin Liu, Jun Zhao, Jiayi Zhao, Ran Meng, Rui Pu, Yiwei Shi and 5 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Zishuai Li *Department of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Chao Fu *Department of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Yifan Chen *Department of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Letian Fang *Department of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Wenbin Liu *Department of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Jun ZhaoDepartment of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China.
Jiayi ZhaoDepartment of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Ran MengDepartment of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Rui PuDepartment of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Yiwei ShiDepartment of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Hongsen ChenDepartment of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Yida HeDepartment of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Yi JinDepartment of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Yibo DingDepartment of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China.
Guangwen CaoDepartment of Epidemiology, Faculty of Navy Medicine, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, China. gcao@smmu.edu.cn.ORCID 0000-0002-8094-1278

Funding

3-year public health program of Shanghai Municipal Health Commission GWVI-11.1-10National 2030 Key Research Program of China 2023ZD0500100National Natural Science Foundation of China 82473715
6 · The paper itself

Abstract

backgroundPatient-derived organoids provide a powerful platform for elucidating mechanisms of drug resistance and tumor evolution in hepatocellular carcinoma (HCC) and identifying novel therapeutic targets.

methodsTranscriptomic sequencing was used to compare gene expression patterns between organoid-forming and non-forming HCC tissues, as well as between sorafenib-resistant organoids and sorafenib-sensitive counterparts. The TCGA-liver hepatocellular carcinoma (LIHC) cohort was used to screen for the key molecular drivers of HCC evolution from the overlapping differentially expressed genes. The effects of D-amino acid oxidase (DAO) on the growth, migration, invasion, apoptosis, and generation of H

resultsExpression level of DAO was significantly downregulated in HCC tissues that successfully formed organoids compared to those that failed, as well as in sorafenib-resistant organoids versus their parental counterparts. In the TCGA-LIHC cohort, DAO expression was significantly reduced in advanced-stage HCC tissues and was inversely correlated with stemness- and epithelial-mesenchymal transition (EMT)-related molecules. Lower DAO expression was associated with poor overall survival in patients with HCC. In HepG2 cells, DAO knockdown significantly enhanced cell proliferation. Ectopic DAO expression suppressed proliferation, migration, and invasion in HepG2 and SK-Hep-1 cells. D-alanine (D-Ala) supplementation further enhanced the anti-proliferative effect of overexpressed DAO, but did not significantly alter the DAO-mediated suppression of migration or invasion. Ectopic expression of DAO induced apoptosis via the generation of H

conclusionDAO appears to be a novel endogenous stemness repressor. The reduction in DAO is a critical molecular event in the evolution of HCC. Therapeutically, combined DAO and D-amino acid supplementation is a promising strategy for HCC treatment, particularly for reversing sorafenib resistance.

Indexed as

Amino AcidsCarcinoma, HepatocellularD-Amino-Acid OxidaseLiver NeoplasmsAnimalsApoptosisCell Line, TumorCell MovementCell ProliferationDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHep G2 CellsHumansMiceAmino AcidsD-Amino-Acid OxidaseSorafenibD-amino acid oxidaseHepatocellular carcinomaHydrogen peroxidePatient-derived organoids

Identifiers

PMID41299678
PMCPMC12659175

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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.