Evidence map›Paper›PMID 40233044›Full record

SynthesisPloS one2025

The role of ANGPTL4 in cancer: A meta-analysis of observational studies and multi-omics investigation.

Osama M Younis, Abdalrahman S Dhaydel, Wasfi F Alghwyeen, Noor R Abu Hantash, Leen M Allan, Issam M Qasem, Anwaar Saeed

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Integrated analysis of scRNA-seq and bulk RNA-seq identifies matrisome-related biomarkers for prognostic stratification and immune landscape in lung adenocarcinoma.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026
    Article
  3. Review
  4. Article
  5. 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

7 authors.

Osama M YounisDivision of Hematology & Oncology, Department of Medicine, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, United States of America.ORCID 0009-0004-1027-554X
Abdalrahman S DhaydelSchool of Medicine, The Hashemite University, Al Zarqaa, Jordan.
Wasfi F AlghwyeenSchool of Medicine, The University of Jordan, Amman, Jordan.
Noor R Abu HantashSchool of Medicine, The University of Jordan, Amman, Jordan.
Leen M AllanSchool of Medicine, The Hashemite University, Al Zarqaa, Jordan.
Issam M QasemSchool of Medicine, Yarmouk University, Irbid, Jordan.
Anwaar SaeedDivision of Hematology & Oncology, Department of Medicine, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, United States of America.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAngiopoietin-like protein 4 (ANGPTL4) plays a crucial role in processes such as angiogenesis, inflammation, and metabolism. Despite numerous studies suggesting its involvement in cancer, a definitive role remains unclear. We introduce the first comprehensive meta-analysis and pan-cancer bioinformatics study on ANGPTL4, aiming to unravel its implications across various cancer types.

methodsModerate-to high-quality observational studies were retrieved from PubMed, Scopus, and Embase. A meta-analysis was conducted using the R package "meta." Survival analysis was performed using GEPIA2 and TIMER2.0. Immune infiltration, mutational burden, and drug resistance analyses was done via GSCAlite. Co-expression and gene set enrichment analyses (GSEA) were carried out using cBioportal and enrichr, respectively.

resultsIncreased ANGPTL4 expression was linked to worse tumor grade (OR =  1.51, P = 0.023), stage (OR =  2.42, P < 0.001), lymph node metastasis (OR =  1.76, P = 0.012), vascular invasion (OR =  2.16, P = 0.01), and lymphatic invasion (OR =  2.20, P < 0.001). Furthermore, ANGPTL4 expression was linked to worse OS (HR = 1.40, 95% CI: 1.29,1.50, P = 0.0001). Single gene level analysis revealed that ANGPTL4 upregulated epithelial-to-mesenchymal transition (EMT) in 23 different cancers. Immune infiltration varied between cancer types, but increased infiltration of cancer-associated fibroblasts was observed in most cancers. Mutation analysis revealed increased alterations in TP53 and CDKN2A in cohorts with ANGPTL4 alterations. GSEA of co-expressed genes revealed involvement in hypoxia, EMT, VEGF-A complex, TGF-B pathways, and extracellular matrix organization.

conclusionsANGPTL4 plays a significant role in tumor progression via its positive regulation of EMT and angiogenesis, while possibly harboring a TGF-B dependent role in systemic metastasis. Therefore, ANGPTL4 is a suitable target for future drug development.

Indexed as

Angiopoietin-Like Protein 4NeoplasmsBiomarkers, TumorComputational BiologyGene Expression Regulation, NeoplasticHumansMultiomicsObservational Studies as TopicAngiopoietin-Like Protein 4ANGPTL4 protein, humanBiomarkers, Tumor

Identifiers

PMID40233044
PMCPMC11999138

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LicenceCC BY
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Registered trials

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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.