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ORIGINAL RESEARCH article
Front. Genet.
Sec. Computational Genomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1549541
This article is part of the Research Topic Machine Learning in Single-Cell Transcriptomics View all articles
Single-cell transcriptomic construction of fibroblast score for analysis of immune infiltration in primary and metastatic ovarian cancer
Provisionally accepted- The Affiliated Hospital of Southwest Medical University, Luzhou, China
Purpose: Ovarian cancer (OV) is a malignant gynecologic cancer with poor clinical outcomes and poor prognosis. The aim of this study was to explore the immune infiltration between primary and metastatic ovarian cancer and the function of fibroblast differential marker in ovarian cancer immunomodulation.Methods: Obtained single-cell transcriptome datasets of primary ovarian cancer and metastatic ovarian cancer, performed cell communication analysis and enrichment analysis. Constructed a new fibroblast score, constructed a prognostic model, screened for prognostically relevant fibroblast differential markers, and analyzed the role of differential markers in immune infiltration of ligand-receptor cells.Results: Single-cell data analysis of ovarian cancer revealed the existence of intercellular communication between fibroblasts and mononuclear macrophages. COX one-way analysis of 28 differential genes in ovarian cancer fibroblasts yielded five genes with prognostic significance for ovarian cancer, and a new Fib score constructed on the basis of these five genes accurately predicted the prognosis of ovarian cancer patients. Further analysis of these five genes revealed that TIMP3 in ovarian cancer fibroblasts affected tumor prognosis, immunosuppression, and drug resistance by targeting M2-type macrophages through the regulation of the CXCL12/CXCR4 signaling axis, which was specifically shown that the higher the expression of TIMP3, the worse the prognosis, the more significant the immune infiltration, and the more drug-resistant the ovarian cancer was.Conclusion：In metastatic ovarian cancer, fibroblasts induce macrophage polarization through the TIMP3-regulated CXCL signaling pathway, which affects the prognosis of ovarian cancer patients and drug resistance of ovarian cancer cells.
Keywords: ovarian cancer, Immune infiltration, Fibroblast Score, Single-cell transcriptome, TIMP3
Received: 21 Dec 2024; Accepted: 27 Mar 2025.
Copyright: © 2025 Ye, Ding and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qinlin Zheng, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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