Evidence map›Paper›PMID 40329370›Full record

ArticleGenome medicine2025

Multi-omics analysis reveals immunosuppression in oesophageal squamous cell carcinoma induced by creatine accumulation and HK3 deficiency.

Yingzhen Gao, Siyu He, Xiaoyan Meng, Kun Zheng, Heyang Cui, Yikun Cheng, Xinyuan Shen, Yuanfang Zhai, Binbin Zou, Fang Wang and 15 more

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Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Molecular subtyping-guided precision therapy for ESCC: biomarker-driven strategies and clinical translation pathways.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  2. Review
  3. Mast cell driven immunometabolism as a therapeutic entry point in ESCC.Frontiers in cell and developmental biology · 2026
    Review
  4. Review
  5. Article
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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

25 authors.

Yingzhen Gao *School of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Siyu He *National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Xiaoyan Meng *School of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Kun Zheng *National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Heyang Cui *Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, SAR, Hong Kong, China.
Yikun ChengDepartment of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, SAR, Hong Kong, China.
Xinyuan ShenSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Yuanfang ZhaiSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Binbin ZouSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Fang WangSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Hongyi LiSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Pengzhou KongSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Yanqiang WangSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Xuefei FengSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Bin YangDepartment of Thoracic Surgery, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, 030013, China.
Ruifang SunDepartment of Tumor Biobank, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, 030013, China.
Yongsheng MengDepartment of Tumor Biobank, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, 030013, China.
Enwei XuDepartment of Pathology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, 030013, China.
Yanlin GuoSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Ning DingCancer Institute, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center, Shenzhen, 518000, China.
Weimin ZhangSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Xiaolong ChengSchool of Basic Medicine, Institute for Pathogenesis and Clinical Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, 030001, China. chengxl@sxmu.edu.cn.
Lunzhi DaiNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. lunzhi.dai@scu.edu.cn.
Yongping CuiCancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030032, China. cuiyp@sxmu.edu.cn.
Ling ZhangCancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030032, China. zhanglingty@sxmu.edu.cn.

Funding

National Key Research and Development Program of China 2021YFC2501001National Natural Science Foundation of China 82103143National Natural Science Foundation of China 82172930National Natural Science Foundation of China 82302916National Natural Science Foundation of China 82394411National Natural Science Foundation of China U21A20372Shanxi Province Higher Education "Billion Project" Science and Technology Guidance Project BYJL005the Science and Technology Achievements Transformation Project of Shanxi Province 202204021301062the Science and Technology Innovation Team of Shanxi Province 202204051001024the Shenzhen Medical Research Fund C2303002the Special Fund for Science and Technology Innovation Teams of Shanxi Province 201605D131045-16the West China Hospital 135 project ZYYC23013
6 · The paper itself

Abstract

backgroundDeep insights into the metabolic remodelling effects on the immune microenvironment of oesophageal squamous cell carcinoma (ESCC) are crucial for advancing precision immunotherapies and targeted therapies. This study aimed to provide novel insights into the molecular landscape of ESCC and identify clinically actionable targets associated with immunosuppression driven by metabolic changes.

methodsWe performed metabolomic and proteomic analyses combined with previous genomic and transcriptomic data, identified multi-omics-linked molecular features, and constructed metabolic-immune interaction-based ESCC classifiers in a discovery cohort and an independent validation cohort. We further verified the molecular characteristics and related mechanisms of ESCC subtypes.

resultsOur integrated multi-omics analysis revealed dysregulated proteins and metabolic imbalances characterizing ESCC, with significant alterations in metabolites and proteins linked to genetic traits. Importantly, ESCC patients were stratified into three subtypes (S1, S2, and S3) on the basis of integrated metabolomic and proteomic data. A robust subtype prediction model was developed and validated across two independent cohorts. Notably, patients classified under the poorest prognosis subtype (S3 subtype) exhibited a significant immunosuppressive microenvironment. We identified key metabolism-related biomarkers for the S3 subtype, specifically creatine and hexokinase 3 (HK3). Creatine accumulation and HK3 protein deficiency synergistically reprogrammed macrophage metabolism, driving M2-like TAM polarization. This metabolic shift fostered an immunosuppressive microenvironment that accelerated tumour progression. These results highlight the potential of targeting creatine metabolism to improve the efficacy of immunotherapy and targeted therapy for ESCC.

conclusionsOur analysis reveals molecular variation in multi-omics linkages and identifies targets that reverse the immunosuppressive microenvironment through metabolic remodelling improving immunotherapy and targeted therapy for ESCC.

Indexed as

CreatineEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaHexokinaseImmune ToleranceFemaleHumansMaleMetabolomicsMultiomicsPrognosisProteomicsTumor MicroenvironmentCreatineHexokinaseCreatineHexokinase 3Immunosuppressive microenvironmentMetabolomicsMulti-omicsOesophageal squamous cell carcinomaProteomicsSubtypes

Identifiers

PMID40329370
PMCPMC12057037

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LicenceCC BY-NC-ND
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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.