m7G 相关肿瘤微环境细胞调控下鼻咽癌的肿瘤相关特征和免疫失调。

IF 2.5 3区 医学 Q3 ONCOLOGY
Zhen Long, Xiaochen Li, Wenmin Deng, Yan Tan, Jie Liu
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引用次数: 0

摘要

背景:鼻咽癌是一种发病率很高的恶性肿瘤。N7-甲基鸟苷(m7G)水平异常与肿瘤进展密切相关。然而,与 m7G 修饰相关的鼻咽癌肿瘤微环境(TME)的特征仍不清楚:方法:根据61个m7G RNA修饰调节因子,采用非负矩阵因式分解算法对来自11个鼻咽癌肿瘤样本和3个鼻咽淋巴增生(NLH)样本的单细胞RNA测序数据中的68795个单细胞进行聚类:结果:在鼻咽癌的TME细胞中发现了m7G调节因子的差异表达,与非鼻咽癌组织相比,鼻咽癌组织中大多数m7G相关免疫细胞群的丰度更高。具体而言,鼻咽癌中CD4+和CD8+ T细胞群的m7G得分明显低于非鼻咽癌组织。T细胞集群对免疫共刺激物和共抑制物的表达存在差异。巨噬细胞集群不同程度地表达了EIF4A1,EIF4A1的高表达与头颈部鳞状细胞癌患者的不良生存率有关。与非鼻咽癌组织相比,EIF4A1在鼻咽癌组织中上调,且主要在CD86+巨噬细胞中表达。此外,在 m7G 相关基因的调控下,鼻咽癌中的 B 细胞集群表现出肿瘤生物学特征。成纤维细胞集群与上述免疫细胞集群相互作用,并丰富了肿瘤生物学通路,如 FGER2 信号通路。重要的是,上皮细胞与 m7G 相关的 TME 细胞集群之间通过各种配体-受体联系存在相关性和相互作用:我们的研究揭示了在 m7G 相关 TME 细胞调控下鼻咽癌微环境中的肿瘤相关特征和免疫失调。这些结果证明了 m7G 在鼻咽癌中的潜在调控作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tumor-associated characteristics and immune dysregulation in nasopharyngeal carcinoma under the regulation of m7G-related tumor microenvironment cells.

Background: Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor progression. However, the characteristics of the tumor microenvironment (TME) in NPC associated with m7G modification remain unclear.

Methods: A total of 68,795 single cells from single-cell RNA sequencing data derived from 11 NPC tumor samples and 3 nasopharyngeal lymphatic hyperplasia (NLH) samples were clustered using a nonnegative matrix factorization algorithm according to 61 m7G RNA modification regulators.

Results: The m7G regulators were found differential expression in the TME cells of NPC, and most m7G-related immune cell clusters in NPC tissues had a higher abundance compared to non-NPC tissues. Specifically, m7G scores in the CD4+ and CD8+ T cell clusters were significantly lower in NPC than in NLH. T cell clusters differentially expressed immune co-stimulators and co-inhibitors. Macrophage clusters differentially expressed EIF4A1, and high EIF4A1 expression was associated with poor survival in patients with head and neck squamous carcinoma. EIF4A1 was upregulated in NPC tissues compared to the non-NPC tissues and mainly expressed in CD86+ macrophages. Moreover, B cell clusters exhibited tumor biological characteristics under the regulation of m7G-related genes in NPC. The fibroblast clusters interacted with the above immune cell clusters and enriched tumor biological pathways, such as FGER2 signaling pathway. Importantly, there were correlations and interactions through various ligand-receptor links among epithelial cells and m7G-related TME cell clusters.

Conclusion: Our study revealed tumor-associated characteristics and immune dysregulation in the NPC microenvironment under the regulation of m7G-related TME cells. These results demonstrated the underlying regulatory roles of m7G in NPC.

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来源期刊
CiteScore
4.70
自引率
15.60%
发文量
362
审稿时长
3 months
期刊介绍: World Journal of Surgical Oncology publishes articles related to surgical oncology and its allied subjects, such as epidemiology, cancer research, biomarkers, prevention, pathology, radiology, cancer treatment, clinical trials, multimodality treatment and molecular biology. Emphasis is placed on original research articles. The journal also publishes significant clinical case reports, as well as balanced and timely reviews on selected topics. Oncology is a multidisciplinary super-speciality of which surgical oncology forms an integral component, especially with solid tumors. Surgical oncologists around the world are involved in research extending from detecting the mechanisms underlying the causation of cancer, to its treatment and prevention. The role of a surgical oncologist extends across the whole continuum of care. With continued developments in diagnosis and treatment, the role of a surgical oncologist is ever-changing. Hence, World Journal of Surgical Oncology aims to keep readers abreast with latest developments that will ultimately influence the work of surgical oncologists.
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