Evidence mapPaperPMID 41235343Full record

ArticleHuman mutation2025

Glucokinase Regulatory Protein (GCKR) Links Metabolic Reprogramming With Immune Exclusion: Insights From a Pan-Cancer Analysis and Gastric Cancer Validation.

Shaohua Fan, Youfu He, Zhen Chen, Chiting Yuan, Jiangjie Chen, Chenhao Xu, Weixing Huang, Can Yao, Dun Hong, Liwei Zhang

Abstract read
In one paragraph

Article in Human mutation, 2025. 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

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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. Article
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.

Shaohua FanDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University School of Medicine, Taizhou, China.ORCID https://orcid.org/0009-0005-5031-8724
Youfu HeDepartment of Cardiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China.ORCID https://orcid.org/0000-0003-4926-1706
Zhen ChenDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University School of Medicine, Taizhou, China.ORCID https://orcid.org/0009-0008-1712-994X
Chiting YuanDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University School of Medicine, Taizhou, China.ORCID https://orcid.org/0009-0008-6878-6325
Jiangjie ChenDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University School of Medicine, Taizhou, China.ORCID https://orcid.org/0009-0003-5885-6661
Chenhao XuDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University School of Medicine, Taizhou, China.ORCID https://orcid.org/0009-0002-2404-5556
Weixing HuangInstitute of Bone Metabolism, Taizhou Hospital of Zhejiang Province, Zhejiang University School of Medicine, Taizhou, China.ORCID https://orcid.org/0009-0003-5305-4942
Can YaoDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University School of Medicine, Taizhou, China.ORCID https://orcid.org/0009-0003-3514-4231
Dun HongDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University School of Medicine, Taizhou, China.ORCID https://orcid.org/0000-0002-2094-4987
Liwei ZhangDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University School of Medicine, Taizhou, China.ORCID https://orcid.org/0000-0002-0515-9841

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glucokinase regulatory protein (GCKR) is a metabolic regulator implicated in glucose homeostasis, but its genetic and functional roles in cancer remain poorly understood. Through integrated pan-cancer multiomics and experimental analyses, we mapped the expression and mutational landscape of GCKR with a focus on gastric cancer. GCKR expression was downregulated in most tumors but upregulated in subsets such as kidney renal papillary carcinoma (KIRP) and lung adenocarcinoma (LUAD). Genomic profiling revealed recurrent alterations, with the highest mutation frequencies observed in sarcoma (SARC) and uterine corpus endometrial carcinoma (UCEC), and missense mutations representing the predominant variant type, particularly in breast cancer (BRCA). Functionally, reduced GCKR expression in gastric cancer was associated with an immune-cold phenotype characterized by diminished cytotoxic T cell infiltration, impaired antigen presentation, and metabolic reprogramming. Spatial transcriptomics and single-cell analyses highlighted compartment-specific heterogeneity and links with cancer-associated fibroblasts and macrophages. Clinically, low GCKR expression predicted poorer survival and reduced immunotherapy benefit, while higher expression indicated selective sensitivity to MEK inhibitors including refametinib and PD0325901. These findings define GCKR as both a mutation- and expression-driven biomarker that connects metabolic regulation with immune remodeling, offering translational value for prognosis and precision therapy in gastric cancer.

Indexed as

Adaptor Proteins, Signal TransducingStomach NeoplasmsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingMutationAdaptor Proteins, Signal TransducingGCKR protein, humanCAFgastric cancerGCKRimmune microenvironmentmetabolic reprogrammingmultiomicsprognosisspatial transcriptomics

Identifiers

PMID41235343
PMCPMC12611472

What Socratic holds

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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 Socratic graph.