CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Cancer-associated fibroblasts-derived FMO2 as a biomarker of macrophage infiltration and prognosis in epithelial ovarian cancer.
Cancer-associated fibroblasts-derived FMO2 as a biomarker of macrophage infiltration and prognosis in epithelial ovarian cancer.
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我们的结果阐明了 FMO2 在 EOC 中的促肿瘤作用及其与免疫成分的关联，它可能成为针对 EOC 的基质导向治疗的潜在靶点。
近期分子谱分析显示，癌症相关成纤维细胞（CAFs）对基质重塑和肿瘤进展至关重要。本研究旨在探讨含黄素单加氧酶2（FMO2）在上皮性卵巢癌（EOC）中作为一种新型CAF来源的预后生物标志物的作用。
原代成纤维细胞从EOC样本中分离。检索显微切割和单细胞RNA测序（scRNA-seq）数据集（包括TCGA、GSE9891、GSE63885、GSE118828和GSE178913）以确定表达谱。基因集富集分析（GSEA）用于探索FMO2与基质激活及免疫浸润之间的相关性。FMO2和联合巨噬细胞浸润水平的预测价值在一个独立的EOC队列（n = 113）中得到验证。
我们证明FMO2在肿瘤间质中上调，并与成纤维细胞活化相关。此外，FMO2对EOC患者较差的临床结局具有预测能力。在EOC的间充质亚型中，FMO2定义的标签显示FMO2促进TIL（肿瘤浸润淋巴细胞）的浸润。此外，我们证实了EOC组织中FMO2与CD163+细胞浸润水平呈正相关，并表明FMO2表达与肿瘤间质中CD163+细胞浸润水平的联合可预测较差的总生存期（HR = 3.63，95% CI = 1.93-6.84，p = 0.0008）。此外，FMO2还可基于免疫检查点（如PD-L1和PD1）的表达预测卵巢癌患者的预后。
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.
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).
We demonstrated that FMO2 was upregulated in tumor stroma and correlated with fibroblast activation. Besides, FMO2 had the predictive power for worse clinical outcome of EOC patients. In the mesenchymal subtype of EOC, the FMO2-defined signature revealed that FMO2 contributed to infiltration of tumor-infiltrating 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).
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.
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