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血液中CSF3R髓系来源抑制细胞增加是乳腺癌复发的一个预测指标。

Increased blood CSF3R myeloid-derived suppressor cell is a predictor for breast cancer recurrence.

作者信息

Li Yen-Liang, Chen Chung-Hsing, Lai You-Syuan, Pan Mei-Ren, Hung Wen-Chun

机构信息

National Institute of Cancer Research, National Health Research Institutes Tainan 704, Taiwan.

Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung 807, Taiwan.

出版信息

Am J Cancer Res. 2024 Jun 25;14(6):3171-3185. doi: 10.62347/MUKD2745. eCollection 2024.

Abstract

Early detection of cancer recurrence using specific biomarkers remains a clinically unmet need, although methodologies for monitoring tumor markers, cell-free DNA, and circulating tumor cells have been established for decades. Tumor recurrence develops in metastatic or dormant cancer cells under continuous immune surveillance. Alterations in the population and function of immune cells may contribute to cancer recurrence. Here, we utilized an animal model to imitate breast tumor recurrence after surgical resection and investigated the abundance and gene expression profiles of immune cells using NanoString analysis. Bioinformatic analysis of a published single-cell RNA sequencing database of myeloid-derived suppressor cells (MDSCs) was performed to identify common targets between the two studies. Identified biomarkers were validated using human peripheral blood mononuclear cell (PBMC) datasets. The inhibitory effect of MDSCs on T-cell proliferation was assessed . Our data demonstrated that the number of MDSCs significantly increased during recurrence. Comparison of our NanoString data with a single-cell RNA sequencing dataset of MDSCs in another spontaneous breast cancer model identified colony-stimulating factor 3 receptor ()-positive MDSCs as a potential marker for predicting tumor relapse. We validated our findings using two previously published PBMC databases of patients with breast cancer with or without recurrence and confirmed the elevated MDSC gene signature and expression in patients with tumor recurrence. 35 patients with breast cancer were also included in our study, that patients with higher levels of CSF3R had worse survival. experiments demonstrated that MDSCs exhibited enhanced reactive oxygen species (ROS) levels and robust T-cell suppression ability. We conclude that an increase in MDSCs is a potential biomarker for early detection of tumor recurrence in patients with breast cancer.

摘要

尽管监测肿瘤标志物、游离DNA和循环肿瘤细胞的方法已经建立了数十年,但利用特定生物标志物早期检测癌症复发在临床上仍未得到满足。肿瘤复发发生在持续免疫监视下的转移性或休眠癌细胞中。免疫细胞群体和功能的改变可能导致癌症复发。在这里,我们利用动物模型模拟手术切除后乳腺肿瘤的复发,并使用NanoString分析研究免疫细胞的丰度和基因表达谱。对已发表的髓源性抑制细胞(MDSC)单细胞RNA测序数据库进行生物信息学分析,以确定两项研究之间的共同靶点。使用人类外周血单核细胞(PBMC)数据集对鉴定出的生物标志物进行验证。评估了MDSC对T细胞增殖的抑制作用。我们的数据表明,复发期间MDSC的数量显著增加。将我们的NanoString数据与另一个自发性乳腺癌模型中MDSC的单细胞RNA测序数据集进行比较,确定集落刺激因子3受体(CSF3R)阳性MDSC是预测肿瘤复发的潜在标志物。我们使用两个先前发表的有或无复发的乳腺癌患者PBMC数据库验证了我们的发现,并证实了肿瘤复发患者中MDSC基因特征和CSF3R表达的升高。我们的研究还纳入了35例乳腺癌患者,CSF3R水平较高的患者生存率较差。实验表明,CSF3R+MDSC表现出增强的活性氧(ROS)水平和强大的T细胞抑制能力。我们得出结论,CSF3R+MDSC的增加是乳腺癌患者肿瘤复发早期检测的潜在生物标志物。

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