{
  "abstract": "Background: Cancer-associated fibroblasts (CAFs) and vascular mural cells may shape extracellular matrix organization in colorectal cancer. However, single-cell comparisons are susceptible to unequal cell recovery, ambient RNA, doublets, treatment-stage mixing, and repeated sampling within patients. We investigated fibrovascular remodeling using patients as the inferential unit and distinguished reproducible signals from donor-concentrated and context-dependent findings.\n\nMethods: We reanalyzed a published single-cell RNA sequencing cohort of 22 patients, including 20 with colorectal cancer and 2 with duodenal carcinoma. The primary pericyte analysis included 14 pretreatment matched normal-tumor pairs with at least three pericytes per tissue. We assessed ambient contamination and doublets using DecontX and scDblFinder. CAFs were reclustered at six response-blind resolutions, and the stable parent population was tested by patient-blocked pseudobulk analysis after excluding its dominant donor. Independent CRC single-cell and spatial datasets, a cross-cancer immunotherapy cohort, and TCGA were used for external testing.\n\nResults: After DecontX correction, tumor pericytes had higher ECM6 scores (median paired change 0.309; false discovery rate [FDR] 0.018). Scores were also higher for the matrix stiffness transcriptional proxy (0.277; FDR 0.012) and the hypoxia/angiogenesis transcriptional program (0.255; FDR 0.028). All three signatures remained significant at the five-pericyte threshold (n=13). COL1A1 and FN1 increased in the analysis, although COL1A1 was borderline in the five-cell sensitivity analysis. Response-blind stability analysis identified a 2,983-cell ECM-remodeling CAF population represented in all 22 patients. After excluding P02, patient-blocked pseudobulk analysis in 15 patients showed higher matrix, inflammatory, and myCAF-related programs and a lower iCAF program. Neither SPP1 nor baseline enrichment in stable disease was supported. In GSE205506, a disjoint 10-gene fibroblast gate retained higher inflammatory and composite CAF scores in non-pCR samples. The highest-scoring unsupervised cluster was donor-concentrated and showed no patient-level association with response. Spatial and cross-cancer analyses yielded mixed or null results.\n\nConclusions: These results support pretreatment fibrovascular transcriptional remodeling at the patient level. They do not establish an SPP1-high response biomarker, a mechanical stiffness phenotype, or causal CAF-to-pericyte signaling. Donor-aware analysis places the rare-cluster observation within a broader, reproducible ECM-remodeling CAF program while defining its evidential limits.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hepatobiliary and Pancreatic Surgery, Ward I, Jingmen Central Hospital, Jingmen Central Hospital affiliated to Jingchu University of Technology , , ,",
    "Operating Room, Jingmen Central Hospital, Jingmen Central Hospital affiliated to Jingchu University of Technology , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yang Gu"
    },
    {
      "affs": [
        1
      ],
      "name": "Li Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuxian Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jie Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhigang Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaofeng Luo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b357hbagmjdpd.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1961075",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668821/?tool=EBI",
  "id": "b357hbagmjdpd",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13668821",
  "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": [
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7215065061",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668821/pdf/?tool=EBI",
  "pmcid": "PMC13668821",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/b357hbagmjdpd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:25Z",
      "native_id": "PMC:PMC13668821",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13668821"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1961075",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1961075/full"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Patient-aware single-cell analysis of fibrovascular remodeling in a predominantly colorectal cancer immunotherapy cohort",
  "title_text": "Patient-aware single-cell analysis of fibrovascular remodeling in a predominantly colorectal cancer immunotherapy cohort",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/b357hbagmjdpd",
  "venue": "Frontiers in immunology",
  "versions": []
}