4.6 Article

Cancer-associated fibroblasts-derived FMO2 as a biomarker of macrophage infiltration and prognosis in epithelial ovarian cancer

期刊

GYNECOLOGIC ONCOLOGY
卷 167, 期 2, 页码 342-353

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2022.09.003

关键词

FMO2; Cancer-associated fibroblasts; Epithelial ovarian cancer; Tumor microenvironment; Macrophage

资金

  1. Natural Science Foundation of Shanghai [22ZR1450700]
  2. National Natural Science Foundation of China [81971340, 81502230]

向作者/读者索取更多资源

This study revealed the tumor-supporting role of FMO2 and its association with immune components in epithelial ovarian cancer. It provides a potential target for stroma-oriented therapies against epithelial ovarian cancer.
Objective. Recent molecular profiling revealed that cancer- associated fibroblasts (CAFs) are essential for matrix remodeling and tumor progression. Our study aimed to investigate the role of flavin-containing monooxygenase 2 (FMO2) in epithelial ovarian cancer (EOC) as a novel CAF-derived prognostic biomarker. Methods. Primary fibroblasts were isolated from EOC samples. Microdissection and single-cell RNA sequencing (scRNA-seq) datasets (including TCGA, GSE9891, GSE63885, GSE118828 and GSE178913) were retrieved to determine the expression profiles. Gene set enrichment analysis (GSEA) was used to explore the correlation between FMO2 and stromal activation as well as immune infiltration. The predictive value of FMO2 and combined macrophage infiltration level was verified in an independent EOC cohort (n= 113). Results. We demonstrated that FMO2 was upregulated in tumor stroma and correlated with fibroblast activation. Besides, FMO2 had the predictive power forworse clinical outcome of EOC patients. In the mesenchymal subtype of EOC, the FMO2-defined signature revealed that FMO2 contributed to infiltration of tumorinfiltrating lymphocytes. Moreover, we confirmed the positive correlation between FMO2 and CD163+ cell infiltration level in EOC tissues, and showed that combination of FMO2 expression with CD163+ cell infiltration level in the tumor stroma could predict poor overall survival (HR = 3.63, 95% CI = 1.93-6.84, p = 0.0008). Additionally, FMO2 also predicted the prognosis of patients with ovarian cancer based on the expression of immune checkpoints (such as PD-L1 and PD1). Conclusion. Our results address the tumor-supporting role of FMO2 in EOC and its association with immune components, and it might be a prospective target for stroma-oriented therapies against EOC. (c) 2022 Elsevier Inc. All rights reserved.

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