Evidence map›Paper›PMID 42174112›Full record

ArticleOncogene2026

GPX8

Qinsi Wan, Jie Li, Mengzhou Guo, Jiahao Hu, Liangliang Bai, Meixia Zhang, Bimin Li, Yuan Fang, Xiaojing Du, Xingxing Zhang and 6 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 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

16 authors.

Qinsi Wan *Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Jie Li *Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Mengzhou Guo *Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
Jiahao HuDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Liangliang BaiDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Meixia ZhangDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Bimin LiDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Yuan FangDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Xiaojing DuEndoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Xingxing ZhangDepartment of Gastroenterology, Shanghai JiaoTong University Affiliated Sixth People's Hospital South Campus, Shanghai, China.
Li SongDepartment of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sinuo ChenLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Zhuoran QiLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Jinglin XiaLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China. xiajinglin@fudan.edu.cn.ORCID http://orcid.org/0000-0001-9443-7075
Bei LvDepartment of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China. lv.bei@zs-hospital.sh.cn.
Mingyan HeDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. ndyfy05035@ncu.edu.cn.ORCID http://orcid.org/0009-0004-0086-8165

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAFs) are necessary constituents of the tumor microenvironment, significantly promoting cancer cell proliferation, invasion, and therapeutic resistance through the secretion of various factors. This study elucidates a novel metabolic-epigenetic mechanism by which glutathione peroxidase 8-positive (GPX8⁺) CAFs confer lenvatinib resistance in hepatocellular carcinoma (HCC). We demonstrate that GPX8 overexpression in CAFs activates the PI3K/AKT/mTOR signaling pathway by suppressing endoplasmic reticulum stress, driving glycolytic reprogramming and lactate production. HCC cells import this CAF-derived lactate via monocarboxylate transporter 1 (MCT1), elevating histone H3 lysine 18 lactylation (H3K18la) levels. Increased H3K18la enrichment at the promoter of bromodomain and PHD finger-containing protein 1 (BRPF1) transcriptionally upregulates BRPF1 expression. Furthermore, we found that BRPF1 mediates lenvatinib resistance in HCC by promoting H3K14ac and inducing activation of the EGFR pathway. Pharmacological inhibition of MCT1 (AZD3965) or BRPF1 (GSK5959), effectively reversed lenvatinib resistance in vitro and in vivo. These findings establish the GPX8⁺ CAF/lactate/MCT1/H3K18la/BRPF1/EGFR axis as a pivotal driver of lenvatinib resistance and identify MCT1 and BRPF1 as actionable therapeutic targets for overcoming resistance in HCC.

Indexed as

Adaptor Proteins, Signal TransducingCancer-Associated FibroblastsCarcinoma, HepatocellularGlutathione PeroxidaseLactic AcidLiver NeoplasmsAnimalsCell Line, TumorDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHistonesHumansLysineMetabolic ReprogrammingMiceMice, NudeAdaptor Proteins, Signal TransducingGlutathione PeroxidaseHistonesLactic AcidLysineMonocarboxylate Transport Protein 1Monocarboxylic Acid TransportersPhenylurea CompoundsQuinolinesSymporters

Identifiers

PMID42174112

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.