Evidence map›Paper›PMID 42048995›Full record

ArticleEBioMedicine2026

Integrated spatial multi-omics delineates fatty acid degradation fuels malignant evolution at the tumour periphery in cervical squamous cell carcinoma.

Shitong Lin, Zhihui Luo, Yuting Li, Bai Hu, Minghan Qu, Binghan Liu, Canhui Cao, Ting Peng, Miaochun Xu, Yashi Xu and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 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

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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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

22 authors.

Shitong LinDepartment of Obstetrics and Gynaecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China.
Zhihui LuoDepartment of Biology and Genetics, The College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, China.
Yuting LiDepartment of Obstetrics and Gynaecology, National Clinical Research Centre for Obstetrics and Gynaecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Bai HuDepartment of Obstetrics and Gynaecology, National Clinical Research Centre for Obstetrics and Gynaecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumour Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Minghan QuDepartment of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Binghan LiuDepartment of Obstetrics and Gynaecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China.
Canhui CaoDepartment of Obstetrics and Gynaecology, National Clinical Research Centre for Obstetrics and Gynaecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumour Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ting PengDepartment of Obstetrics and Gynaecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China.
Miaochun XuDepartment of Obstetrics and Gynaecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China.
Yashi XuDepartment of Obstetrics and Gynaecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China.
Xiaojie LiuDepartment of Obstetrics and Gynaecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China.
Xiaoli WangDepartment of Obstetrics and Gynaecology, National Clinical Research Centre for Obstetrics and Gynaecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumour Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Li LiDepartment of Obstetrics and Gynaecology, National Clinical Research Centre for Obstetrics and Gynaecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumour Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wencheng DingDepartment of Obstetrics and Gynaecology, National Clinical Research Centre for Obstetrics and Gynaecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumour Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhenyu XuShanghai Lu Ming Biotech Co., Ltd., Shanghai, China.
Ruizhi LiShanghai Lu Ming Biotech Co., Ltd., Shanghai, China.
Jingwei ZhaoDepartment of Biology and Genetics, The College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, China.
Jingmin ZhangHubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
Lingfang WangZhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynaecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: 11818387@zju.edu.cn.
Fang RenDepartment of Gynaecology, First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, Henan, China. Electronic address: renfang@foxmail.com.
Chaolong WangDepartment of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: chaolong@hust.edu.cn.
Peng WuDepartment of Obstetrics and Gynaecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China. Electronic address: pengwu8626@tjh.tjmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCervical squamous cell carcinoma (CSCC) exhibits profound spatial heterogeneity in evolutionary trajectories across distinct tumour foci, yet the underlying mechanisms remain poorly understood.

methodsIn this study, we performed an integrated spatial transcriptomic and metabolomic analysis of six CSCC and two normal cervical samples, supported by single-cell RNA sequencing (n = 20) and validated in an independent spatial enhanced resolution omics-sequencing cohort (n = 15), to map the spatial tumour architecture and cellular heterogeneity of CSCC. Findings were functionally confirmed using cell lines, patient-derived organoids, and mouse models.

findingsWe identified that tumour foci with high spatial continuity demonstrated elevated cancer cell purity and exhibited distinct spatial stratification. The peripheral tumour foci (layer 3) exhibited enhanced proliferative capacity and aggressive traits characterised by elevated epithelial-to-mesenchymal transition (EMT) activity compared to core foci (layer 1), which correlated with advanced evolutionary states. A layer 3-specific gene signature predicted poorer overall survival in both the Cancer Genome Atlas (TCGA) and Tongji Hospital (TJH) cohorts. Spatial multi-omics uncovered progressive metabolic reprogramming along the core-to-periphery axis, with activation of fatty acid degradation emerging as a hallmark of layer 3 aggression. Genetic knockdown (HADH, HADHA and ECHS1) and pharmacological inhibition (mitotane and perhexiline) of fatty acid degradation attenuated malignant phenotypes of layer 3, including proliferation and EMT-driven invasion.

interpretationOur work establishes spatially resolved activation of the fatty acid degradation as a key evolutionary engine fuelling the malignant phenotypes of peripheral tumour foci, and nominates stratification-targeted metabolic disruption as a spatially promising therapeutic strategy for CSCC.

fundingNoncommunicable Chronic Diseases-National Science and Technology Major Project (2025ZD0544100), National Natural Science Foundation of China (82372929, 82503148, 32300460, 32400555 and 82472696), China Postdoctoral Science Foundation (2025M772119), Hubei Provincial Natural Science Foundation (JCZRQN202500308).

Indexed as

Carcinoma, Squamous CellFatty AcidsUterine Cervical NeoplasmsAnimalsCell Line, TumorEpithelial-Mesenchymal TransitionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingMetabolomicsMiceMultiomicsSpatial TranscriptomicsFatty AcidsCSCCEMTFatty acid degradationSpatial metabolomicsSpatial transcriptomics

Identifiers

PMID42048995
PMCPMC13137026

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