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用于分析原发性和转移性卵巢癌免疫浸润的成纤维细胞评分的单细胞转录组构建

Single-cell transcriptomic construction of fibroblast score for analysis of immune infiltration in primary and metastatic ovarian cancer.

作者信息

Guo Qian, Ding Hongmei, Zheng Qinlin

机构信息

Obstetrics and Gynecology Department, The Affiliated Hospital of Southwest Medical University, LuZhou, China.

出版信息

Front Genet. 2025 Apr 28;16:1549541. doi: 10.3389/fgene.2025.1549541. eCollection 2025.

DOI:10.3389/fgene.2025.1549541
PMID:40357367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12066613/
Abstract

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.

摘要

目的

卵巢癌（OV）是一种临床结局和预后较差的妇科恶性肿瘤。本研究旨在探讨原发性和转移性卵巢癌之间的免疫浸润情况以及成纤维细胞差异标志物在卵巢癌免疫调节中的作用。

方法

获取原发性卵巢癌和转移性卵巢癌的单细胞转录组数据集，进行细胞间通讯分析和富集分析。构建新的成纤维细胞评分，构建预后模型，筛选与预后相关的成纤维细胞差异标志物，并分析差异标志物在配体-受体细胞免疫浸润中的作用。

结果

卵巢癌的单细胞数据分析揭示了成纤维细胞与单核巨噬细胞之间存在细胞间通讯。对卵巢癌成纤维细胞中的28个差异基因进行COX单因素分析，得到5个对卵巢癌具有预后意义的基因，基于这5个基因构建的新Fib评分能够准确预测卵巢癌患者的预后。对这5个基因的进一步分析表明，卵巢癌成纤维细胞中的TIMP3通过调节CXCL12/CXCR4信号轴靶向M2型巨噬细胞，从而影响肿瘤预后、免疫抑制和耐药性，具体表现为TIMP3表达越高，预后越差，免疫浸润越显著，卵巢癌耐药性越强。

结论

在转移性卵巢癌中，成纤维细胞通过TIMP3调节的CXCL信号通路诱导巨噬细胞极化，影响卵巢癌患者的预后和卵巢癌细胞的耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/745188825c1b/fgene-16-1549541-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/2fd5770ef3fe/fgene-16-1549541-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/69ba353259b3/fgene-16-1549541-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/2123efeedf9d/fgene-16-1549541-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/82f3349810a3/fgene-16-1549541-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/6da9c15f4e8f/fgene-16-1549541-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/745188825c1b/fgene-16-1549541-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/2fd5770ef3fe/fgene-16-1549541-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/69ba353259b3/fgene-16-1549541-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/2123efeedf9d/fgene-16-1549541-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/82f3349810a3/fgene-16-1549541-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/6da9c15f4e8f/fgene-16-1549541-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1370/12066613/745188825c1b/fgene-16-1549541-g006.jpg

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本文引用的文献

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Integration of single-cell RNA-seq and bulk RNA-seq data to construct and validate a cancer-associated fibroblast-related prognostic signature for patients with ovarian cancer.单细胞 RNA 测序和批量 RNA 测序数据的整合，构建和验证卵巢癌患者与癌症相关成纤维细胞相关的预后标志物。
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STING inhibitors sensitize platinum chemotherapy in ovarian cancer by inhibiting the CGAS-STING pathway in cancer-associated fibroblasts (CAFs).STING 抑制剂通过抑制癌症相关成纤维细胞 (CAFs) 中的 CGAS-STING 通路，增强卵巢癌细胞对铂类化疗的敏感性。
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