Ovarian HGSOC Precursor Lesions — GeoMx Spatial Profiling (Gray Foundation 2024)

Overview

Multi-center spatial profiling dataset of 44 FFPE fallopian tube specimens from 43 individuals, spanning precursor lesions (p53 signatures, STICs) to co-occurring invasive high-grade serous ovarian carcinoma (HGSOC). Profiled by NanoString GeoMx whole transcriptome analysis (WTA) and 31-antibody cyclic immunofluorescence (CyCIF). Data integrated into cBioPortal as ovary_geomx_gray_foundation_2024. PMID:39386723

Composition

  • 44 FFPE fallopian tube specimens from 43 individuals from University of Pennsylvania, Swedish Cancer Institute (Seattle), and collaborating sites. PMID:39386723
  • Group 1 (n=24): invasive cancer with co-occurring STIC (STIC.C); 15/24 BRCA WT, 7/9 germline BRCA1, 6/7 germline BRCA2. PMID:39386723
  • Group 2 (n=19): no invasive cancer; incidental p53 signatures (p53.I, n=10) and incidental STICs (STIC.I, n=9) from risk-reducing surgery. PMID:39386723

Assays / panels (linked)

  • NanoString GeoMx whole transcriptome analysis (WTA) across >600 regions of interest in 35/44 specimens. PMID:39386723
  • CyCIF (31-antibody panel) in all 44 specimens; 4.22×10^7 single cells classified into 21 cell neighborhood topics via latent Dirichlet allocation. PMID:39386723

Papers using this cohort

  • PMID:39386723 — Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.

Notable findings derived from this cohort

  • IFN-alpha and IFN-gamma pathway genes (STAT1, IFITM1, IRF9, IRF7, ISG15, TAP1, HLA-A) significantly upregulated beginning at the p53 signature stage and persisting through STIC and invasive cancer. PMID:39386723
  • HLA-E progressively upregulated (p53.I median 4% to STIC.C 26% positive epithelial cells) as an immune evasion mechanism potentially inhibiting NK cell cytotoxicity via NKG2A engagement. PMID:39386723
  • cGAS-STING pathway activation via micronuclear rupture (BANF1-positive ruptured micronuclei with cGAS co-localization) observed as early as STIC.I lesions. PMID:39386723

Sources

  • cBioPortal study ovary_geomx_gray_foundation_2024 PMID:39386723.

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