{ "abstract": "Background: The prognostic relevance of angiogenesis in breast cancer remains unclear when modeled as a coordinated gene program rather than individual gene effects. This study aimed to characterize the multidimensional structure of angiogenesis and assess the prognostic relevance of its latent components for overall survival in breast cancer. Methods: Using RNA sequencing data from 1,096 patients with The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) from the United States, we summarized 36 angiogenesis-related genes via principal component analysis (PCA) applied to standardized log-counts per million values. The first three components (Z1−Z3), retained based on variance explained, scree plot inspection, and interpretable gene loading patterns, were evaluated for association with overall survival using Kaplan-Meier and Cox proportional hazards models adjusted for age and molecular subtype. Results: The first three components captured a multi-dimensional structure of angiogenesis activity. None was significantly associated with overall survival in multivariable Cox models (Z1: HR = 1.016, 95% CI: 0.957–1.078, p = 0.603; Z2: HR = 1.049, 95% CI: 0.954–1.153, p = 0.319; Z3: HR = 1.007, 95% CI: 0.918–1.105, p = 0.878), and Kaplan–Meier analyses showed no significant survival differences across median-based groups. Functional enrichment analyses indicated that the retained components represented distinct biological dimensions of angiogenesis. Subtype-specific analyses showed no statistically significant associations within individual subtypes and no strong evidence of effect modification. However, marked differences in latent component distributions across molecular subtypes revealed substantial subtype-specific heterogeneity. Collectively, these findings indicate limited independent prognostic relevance for overall survival despite substantial biological heterogeneity and subtype-specific variation. Conclusions: Angiogenesis is a multi-dimensional and biologically heterogeneous process. No latent angiogenesis component demonstrated independent prognostic value for overall survival, indicating that angiogenesis is insufficient as a standalone prognostic biomarker. Nevertheless, subtype-specific variation across latent dimensions highlights its relevance for understanding biological heterogeneity in breast cancer.", "abstract_shown": true, "affiliations": [ "Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio, United States of America.", "Department of Mathematics and Statistics, University of New Mexico, Albuquerque, New Mexico, United States of America.", "Department of Statistics and Actuarial Science, University of Ghana, Accra, Ghana." ], "article_type": "Research Article", "arxiv": null, "author_total": 1, "authors": [ { "affs": [ 0, 1, 2 ], "name": "Dennis Baidoo", "orcid": "0009-0006-2719-7730" } ], "bibtex": "https://research.draconitic.com/paper/bxs6cac9tsf1c.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0348390", "fulltext_url": "https://europepmc.org/articles/PMC13722169", "id": "bxs6cac9tsf1c", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0348390", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Angiogenesis" ], [ "heading", "Basic Cancer Research" ], [ "heading", "Biology and Life Sciences" ], [ "heading", "Biology and life sciences" ], [ "heading", "Breast Cancer" ], [ "heading", "Breast Tumors" ], [ "heading", "Cancer Genomics" ], [ "heading", "Cancer Treatment" ], [ "heading", "Cancers and Neoplasms" ], [ "heading", "Cardiovascular Physiology" ], [ "heading", "Cell Biology" ], [ "heading", "Cell biology" ], [ "heading", "Cell signaling" ], [ "heading", "Cellular Structures and Organelles" ], [ "heading", "Developmental Biology" ], [ "heading", "Extracellular Matrix" ], [ "heading", "Gene Expression" ], [ "heading", "Genetics" ], [ "heading", "Genomic Medicine" ], [ "heading", "Genomics" ], [ "heading", "Mathematical and Statistical Techniques" ], [ "heading", "Mathematics" ], [ "heading", "Medicine and Health Sciences" ], [ "heading", "Multivariate Analysis" ], [ "heading", "Oncology" ], [ "heading", "Physical Sciences" ], [ "heading", "Physiology" ], [ "heading", "Principal Component Analysis" ], [ "heading", "Research Article" ], [ "heading", "Research and Analysis Methods" ], [ "heading", "Signal transduction" ], [ "heading", "Statistical Methods" ], [ "heading", "Statistics" ], [ "heading", "VEGF signaling" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular structures and organelles/Extracellular matrix" ], [ "plos", "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/VEGF signaling" ], [ "plos", "/Biology and life sciences/Developmental biology/Angiogenesis" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression" ], [ "plos", "/Biology and life sciences/Genetics/Genomics/Genomic medicine/Cancer genomics" ], [ "plos", "/Biology and life sciences/Physiology/Cardiovascular physiology/Angiogenesis" ], [ "plos", "/Medicine and health sciences/Oncology/Basic cancer research/Cancer genomics" ], [ "plos", "/Medicine and health sciences/Oncology/Cancer treatment" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms/Breast tumors/Breast cancer" ], [ "plos", "/Physical sciences/Mathematics/Statistics/Statistical methods/Multivariate analysis/Principal component analysis" ], [ "plos", "/Research and analysis methods/Mathematical and statistical techniques/Statistical methods/Multivariate analysis/Principal component analysis" ] ], "openalex": null, "pdf_url": "https://europepmc.org/articles/PMC13722169?pdf=render", "pmcid": "PMC13722169", "pmid": "42961931", "published": "2026-10-30", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/bxs6cac9tsf1c.ris", "sources": [ { "first_seen": "2026-10-31T12:20:55Z", "native_id": "10.1371/journal.pone.0348390", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0348390" }, { "first_seen": "2026-11-02T03:21:21Z", "native_id": "MED:42961931", "source": "europepmc", "url": "https://europepmc.org/article/MED/42961931" }, { "first_seen": "2026-11-03T12:22:43Z", "native_id": "PMC13722169", "source": "pmc", "url": "https://doi.org/10.1371/journal.pone.0348390" } ], "subjects": [ { "field": "biochemistry", "origin": "heading:Gene Expression", "subfield": "molecular-biology" }, { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "heading:Developmental Biology", "subfield": "developmental-biology" }, { "field": "mathematics", "origin": "plos:statistical methods", "subfield": "statistics" }, { "field": "medicine", "origin": "plos:oncology", "subfield": "oncology" } ], "title": "Multi-dimensional structure and subtype-specific heterogeneity of angiogenesis in breast cancer", "title_text": "Multi-dimensional structure and subtype-specific heterogeneity of angiogenesis in breast cancer", "type": "peer-reviewed", "updated_at": "2026-11-03T12:22:43Z", "url": "https://research.draconitic.com/paper/bxs6cac9tsf1c", "venue": "PLOS One", "versions": [] }