Evidence map›Paper›PMID 39616302›Full record

ArticleMolecular biomedicine2024

Glycosyltransferase B4GALNT1 promotes immunosuppression in hepatocellular carcinoma via the HES4-SPP1-TAM/Th2 axis.

Zhifeng Wang, Jiaxin Liu, Xiaoming Wang, Qingyun Wu, Qiao Peng, Tianxiao Yang, Xuehui Sun, Xiaofeng Wang, Yilin Wang, Weicheng Wu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular biomedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. The Role of CD4Cells · 2026
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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

10 authors.

Zhifeng Wang *Human Phenome Institute, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Jiaxin Liu *Human Phenome Institute, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Xiaoming Wang *Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
Qingyun WuHuman Phenome Institute, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Qiao PengShanghai Tenth People's Hospital, School of Medicine, Tongji University Cancer Center, Tongji University, Shanghai, China.
Tianxiao YangHuman Phenome Institute, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Xuehui SunHuman Phenome Institute, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Xiaofeng WangHuman Phenome Institute, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Yilin WangDepartment of Hepatic Surgery, Department of Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China. linglingwangyi@126.com.
Weicheng WuHuman Phenome Institute, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China. wuweicheng@fudan.edu.cn.ORCID 0000-0001-5605-3898

Funding

AnHui Province Educational Natural Science Project 2023AH040254¨Climbing Peak¨ Training Program for Innovative Technology team of Yijishan Hospital¸Wannan Medical College KPF2019011National Natural Science Foundation of China 31900568National Natural Science Foundation of China 82473424Science and Technology Committee of Xuhui District 23XHYD-26Shanghai hospital Development Center SHDC2024CRI094Shanghai Municipal Science and Technology Major Project 2017SHZDZX01Shanghai Municipal Science and Technology Major Project 2023SHZDZX02
6 · The paper itself

Abstract

β-1,4-N-acetylgalactosaminyltransferase I (B4GALNT1) is a key glycosyltransferase for gangliosides. Its aberrant expression has been observed in various cancers, and its potential roles in tumor immunity were suggested recently. However, how B4GALNT1 regulate tumor progression and tumor immunity remains largely unknown. In this study, we aimed to investigate the roles of B4GALNT1 in hepatocellular carcinoma (HCC), particularly in reshaping the tumor immune microenvironment, and evaluate the potential beneficial effects of targeting B4GALNT1 in immunotherapy. Our data verified the aberrant upregulation of B4GALNT1 in HCC tumor tissues and tumor cells, which could be utilized as an independent prognostic factor and improve the predicting performance of traditional tumor node metastasis (TNM) system. We also demonstrated that B4GALNT1 increased the phosphorylation of Hes Family BHLH Transcription Factor 4 (HES4) via p38 mitogen-activated protein kinase (p38)/ c-Jun N-terminal kinase (JNK) signaling in tumor cells, thus increasing the transcriptional activity of HES4, which upregulated the synthesis and secretion of secreted phosphoprotein 1 (SPP1), modulated the composition of tumor-associated macrophages (TAMs) and T helper type 2 (Th2) cells, and eventually reshaped the immunosuppressive microenvironment. In addition, silencing B4GALNT1 was proved to enhance the tumor-killing efficiency of the programmed cell death protein 1 (PD-1)-targeting strategy in mouse model. In conclusion, this study evaluated B4GALNT1 as a prognostic predictor for HCC patients and revealed the mechanism of B4GALNT1 in microenvironmental remodeling, which extends the understanding of HCC progression and provides a novel auxiliary strategy for HCC immunotherapy.

Indexed as

Basic Helix-Loop-Helix ProteinsCarcinoma, HepatocellularLiver NeoplasmsN-AcetylgalactosaminyltransferasesTh2 CellsTumor MicroenvironmentAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMiddle AgedPrognosisTumor-Associated MacrophagesBasic Helix-Loop-Helix ProteinsN-AcetylgalactosaminyltransferasesB4GALNT1Hepatocellular carcinomaImmunosuppressionPrognosis

Identifiers

PMID39616302
PMCPMC11608210

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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.