Evidence map›Paper›PMID 38725845›Full record

ArticleInternational journal of biological sciences2024

Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma.

Zhi-Yong Liu, Xia-Hui Lin, Hong-Ying Guo, Xuan Shi, Dan-Ying Zhang, Jia-Lei Sun, Guang-Cong Zhang, Ru-Chen Xu, Fu Wang, Xiang-Nan Yu and 6 more

Abstract read
In one paragraph

Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

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  11. Genetic Polymorphisms ofInternational journal of molecular sciences · 2025
    Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. CD4Trends in cancer · 2024
    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

16 authors.

Zhi-Yong LiuDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Xia-Hui LinDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Hong-Ying GuoDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Xuan ShiDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Dan-Ying ZhangDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Jia-Lei SunDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Guang-Cong ZhangDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Ru-Chen XuDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Fu WangDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Xiang-Nan YuDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Dou WangDepartment of Gastroenterology, Shigatse People's Hospital, Shigatse, Tibet 857000, China.
Shu-Qiang WengDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Xi-Zhong ShenDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Tao-Tao LiuDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Ling DongDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
Ji-Min ZhuDepartment of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysregulation of the aldehyde dehydrogenase (ALDH) family has been implicated in various pathological conditions, including cancer. However, a systematic evaluation of ALDH alterations and their therapeutic relevance in hepatocellular carcinoma (HCC) remains lacking. Herein, we found that 15 of 19 ALDHs were transcriptionally dysregulated in HCC tissues compared to normal liver tissues. A four gene signature, including ALDH2, ALDH5A1, ALDH6A1, and ALDH8A1, robustly predicted prognosis and defined a high-risk subgroup exhibiting immunosuppressive features like regulatory T cell (Tregs) infiltration. Single-cell profiling revealed selective overexpression of tumor necrosis factor receptor superfamily member 18 (TNFRSF18) on Tregs, upregulated in high-risk HCC patients. We identified ALDH2 as a tumor suppressor in HCC, with three novel phosphorylation sites mediated by protein kinase C zeta that enhanced enzymatic activity. Mechanistically, ALDH2 suppressed Tregs differentiation by inhibiting β-catenin/TGF-β1 signaling in HCC. Collectively, our integrated multi-omics analysis defines an ALDH-Tregs-TNFRSF18 axis that contributes to HCC pathogenesis and represents potential therapeutic targets for this aggressive malignancy.

Indexed as

Aldehyde Dehydrogenase, MitochondrialCarcinoma, HepatocellularLiver NeoplasmsT-Lymphocytes, RegulatoryAldehyde DehydrogenaseAnimalsCell Line, TumorHumansMaleMiceMultiomicsTumor MicroenvironmentAldehyde DehydrogenaseAldehyde Dehydrogenase, MitochondrialALDH2 protein, humanALDH2Liver cancerMetabolic disturbanceRegulatory T cellsTNFRSF18 (GITR)

Identifiers

PMID38725845
PMCPMC11077362

What OpenQuestion holds

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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.