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Single-Cell Analysis Links C7+ Cancer-Associated Fibroblasts with Incomplete Resection in Platinum-Sensitive Relapsed

Longxia Li1,2, Shangbing Gao1, Yilizhati Maimaiti1

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A novel cancer-associated fibroblast subpopulation (CAF-C7) hinders complete tumor resection in platinum-sensitive relapsed ovarian cancer (PSROC). Targeting the IGF1-IGF1R pathway may improve surgical outcomes for these patients.

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IGF1-IGF1Rcancer-associated fibroblastsrelapsed ovarian cancersecondary cytoreductive surgery

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Area of Science:

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment Research

Background:

  • Complete resection (R0) is crucial for outcomes in platinum-sensitive relapsed ovarian cancer (PSROC) secondary cytoreduction (SCR).
  • Tumor microenvironment (TME) heterogeneity significantly impacts surgical success in SCR.

Purpose of the Study:

  • To identify TME components influencing R0 resection in PSROC.
  • To elucidate the role of cancer-associated fibroblasts (CAFs) in surgical outcomes for SCR.

Main Methods:

  • Integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics.
  • Functional assays on primary tumor cells.
  • Analysis of TME heterogeneity and CAF subpopulations.

Main Results:

  • Identified a novel CAF-C7 subpopulation enriched in tumors from patients with incomplete resection (non-R0).
  • CAF-C7 promotes tumor cell migration, inhibits anoikis, and enhances angiogenesis via the IGF1-IGF1R axis.
  • Inhibition of the IGF1-IGF1R pathway reduced CAF-C7 pro-tumorigenic functions.

Conclusions:

  • CAF-C7 is a novel cellular driver of poor surgical outcomes in PSROC SCR.
  • The IGF1-IGF1R pathway presents a potential therapeutic target.
  • Findings suggest new biomarkers for patient stratification and treatment strategies.