Evidence map›Paper›PMID 40054660›Full record

ArticleCancer letters2025

The landscape of malignant transition: Unraveling cancer cell-of-origin and heterogeneous tissue microenvironment.

Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Abstract read
In one paragraph

Article in Cancer letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. RMzyme: regulations of RNA-modifying enzymes in humans.Signal transduction and targeted therapy · 2026
    Article
  5. Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026
    Review
  6. Article
  7. Article
  8. Terminally exhausted CD8Frontiers in immunology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Ruihan LuoLaboratory of Hepatic AI Translation, Frontier Science Center for Disease-Related Molecular Network and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, China; Center for Computational Systems Medicine, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA; Med-X Center for Informatics, Sichuan University, Chengdu, 610041, China. Electronic address: 2021324020151@stu.scu.edu.cn.
Jiajia LiuCenter for Computational Systems Medicine, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Tiangang WangCenter for Computational Systems Medicine, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Weiling ZhaoCenter for Computational Systems Medicine, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Yanfei WangCenter for Computational Systems Medicine, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Jianguo WenCenter for Computational Systems Medicine, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Hongyu WangDepartment of Diagnostic and Interventional Imaging, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA; Center for Nursing Research, Cizik School of Nursing, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Shanli DingGraduate School of Biomedical Sciences, The University of MD Anderson Cancer Center, Houston, TX 77030, USA.
Xiaobo ZhouCenter for Computational Systems Medicine, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA; McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. Electronic address: Xiaobo.Zhou@uth.tmc.edu.

Funding

Multiscale Resolution and Deep Network Approaches for Deconvolving Different Cell Types in Bulk Tumor using Single-cell Sequencing Data (scDEC)R01CA241930 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ZHOU, XIAOBO · 2019 to 2023
$2.7M
Optimizing mRNA sequences with deep neural networksR01LM014156 · NLM · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Xiaobo Zhou · 2024 to 2026
$1.1M
Developing mRNAdesigner tool package for optimization of mRNA sequenceR01GM153822 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ZHOU, XIAOBO · 2024 to 2025
$624k
NCI NIH HHS R01 CA241930NIGMS NIH HHS R01 GM153822NLM NIH HHS R01 LM014156
6 · The paper itself

Abstract

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced ANXA1 levels promoted monocyte differentiation toward M1 macrophages and inflammatory responses, whereas during malignant progression, upregulated ANXA1 fostered M2 macrophage polarization and cancer-associated fibroblast transformation by increasing TGF-β production. Our spatiotemporal analysis further provided insights into mechanisms responsible for immunosuppression and a potential target to control evolution of precancer and mitigate the risk for cancer development.

Indexed as

Cell Transformation, NeoplasticNeoplasmsNeoplastic Stem CellsTumor MicroenvironmentCell DifferentiationDisease ProgressionHumansMacrophagesTransforming Growth Factor betaTransforming Growth Factor betaFibroblastsHeterogeneityMacrophagesMicroenvironmentPrecancer-to-cancer transitionStem-like cells

Identifiers

PMID40054660
PMCPMC12040592

What OpenQuestion holds

Textmetadata
LicenceTDM
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.