{
  "abstract": "Background/Objectives: Regional transcriptomic labels can reflect cell mixtures and expression states. We examined how transcriptomically defined cold regions in triple-negative breast cancer relate to matrix-associated expression, annotated composition, spatial neighborhoods, and cell-type attribution. Methods: We reanalyzed public data from 43 discovery sections (22 patients) and 11 cancer captures of a secondary dataset with discovery-derived labels. Computational spot labels included desert (D), excluded (E), inflamed (I), and ambiguous-cold. Hierarchical models estimated E−D contrasts and E−I gene contrasts with and without sequencing-depth and estimated tumor-abundance adjustment; tests underwent Holm correction. Further analyses addressed annotated composition, neighborhoods, and pooled exploratory cell-type attribution. Results: Estimated cancer-associated fibroblast (CAF) abundance was higher in E- than D-labeled regions (standardized within-section effect 0.78; 95% confidence interval 0.55–1.00), as was expression of PDGFRB, COL3A1, COL5A1, and COL6A1; the three collagen genes remained higher than in D- and I-labeled regions after adjustment. Across 11 captures, the median within-capture difference in tumor-annotated spot fraction (E minus D) was −14.1 percentage points (95% bootstrap interval −33.5 to −10.7; nine negative, two ties; interval reached zero without in situ annotations). In discovery, 330 of 822 ambiguous cold spots neighbored both D- and E-labeled spots, exceeding two null models. Pooled models estimated positive COL3A1 and COL5A1 differences within CAFs; immune readouts depended on scoring and adjustment. Conclusions: We characterized a stromal–transcriptomic contrast: E-labeled regions showed higher matrix-associated expression and estimated CAF abundance than D-labeled regions and, in the secondary dataset, lower annotated tumor fraction. These measurements refine interpretation without implying functional immune exclusion.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Transdisciplinary Science & Technology, Siddha Vetha Multiversity, Newark, NJ 07103, USA",
    "NFInnovations, Renton, WA 170129, USA",
    "Centro de Investigación Biomédica (CENBIO), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Av. Mariscal Sucre s/n y Mariana de Jesús, Quito 170129, Ecuador"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "William D. Lituma-Gonzalez"
    },
    {
      "affs": [
        0
      ],
      "name": "Amogh V. Arunprasad"
    },
    {
      "affs": [
        1
      ],
      "name": "Hugo Chancay",
      "orcid": "0009-0008-6300-8575"
    },
    {
      "affs": [
        0
      ],
      "name": "Varshithaa Jayavelan"
    },
    {
      "affs": [
        0
      ],
      "name": "Meenakshi Chakravadhanula"
    },
    {
      "affs": [
        2
      ],
      "name": "Santiago Ballaz",
      "orcid": "0000-0001-5878-8679"
    },
    {
      "affs": [
        0
      ],
      "name": "Shanmugamurthy Lakshmanan",
      "orcid": "0009-0009-4910-439X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6bj0tnn0df09n.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18213476",
  "fulltext_url": null,
  "id": "6bj0tnn0df09n",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/21/3476",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7224114827",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/6bj0tnn0df09n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:58Z",
      "native_id": "10.3390/cancers18213476",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/21/3476"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Matrix-Associated Gene Expression and Annotated Tumor–Stroma Composition of Transcriptomically Defined Cold Regions in Triple-Negative Breast Cancer",
  "title_text": "Matrix-Associated Gene Expression and Annotated Tumor–Stroma Composition of Transcriptomically Defined Cold Regions in Triple-Negative Breast Cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:58Z",
  "url": "https://research.draconitic.com/paper/6bj0tnn0df09n",
  "venue": "Cancers",
  "versions": []
}