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单细胞转录组图谱解析嗅神经母细胞瘤亚型及肿瘤内异质性。

Single-cell transcriptomic landscape deciphers olfactory neuroblastoma subtypes and intra-tumoral heterogeneity.

作者信息

Yang Jingyi, Song Xiaole, Zhang Huankang, Liu Quan, Wei Ruoyan, Guo Luo, Yuan Cuncun, Chen Fu, Xue Kai, Lai Yuting, Wang Li, Shi Junfeng, Zhou Chengle, Wang Juan, Yu Yingxuan, Mei Qibing, Hu Li, Wang Huan, Zhang Chen, Zhang Qianqian, Li Houyong, Gu Ye, Zhao Weidong, Yu Huapeng, Wang Jingjing, Liu Zhuofu, Li Han, Zheng Shixing, Liu Juan, Yang Lu, Li Wanpeng, Xu Rui, Chen Jiani, Zhou Yumin, Cheng Xiankui, Yu Yiqun, Wang Dehui, Sun Xicai, Yu Hongmeng

机构信息

ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai, PR China.

Olfactory Neuroblastoma Diagnosis and Treatment Center, Eye and ENT Hospital, Fudan University, Shanghai, PR China.

出版信息

Nat Cancer. 2024 Dec;5(12):1919-1939. doi: 10.1038/s43018-024-00855-5. Epub 2024 Nov 14.

DOI:10.1038/s43018-024-00855-5
PMID:39543363
Abstract

Olfactory neuroblastoma (ONB) is a rare malignancy known to originate from the olfactory epithelium. The complex tumor ecosystem of this pathology remains unclear. Here, we explored the cellular components within ten ONB tumors and one olfactory mucosa sample based on single-cell RNA profiles. We showed the intra-tumoral heterogeneity by identifying five unique expression programs among malignant epithelial cells. A distinct three-classification system (neural, basal, mesenchymal) for ONB was established according to the distinguished gene expression patterns. Biomarkers for categorizing bulk tumors into uncharacterized subtypes were elucidated. Different responses towards certain chemotherapy regimens could be cautiously inferred according to the molecular features representing the three tumor types, thus helping with precision chemotherapy. We also analyzed subclusters of the tumor microenvironment (TME) and the interactions among different cell types within the TME. The relative abundance of immunosuppressive tumor-associated macrophages suggests potential benefits of immunotherapies targeting macrophages.

摘要

嗅神经母细胞瘤(ONB)是一种已知起源于嗅上皮的罕见恶性肿瘤。这种病理状态下复杂的肿瘤生态系统仍不清楚。在此,我们基于单细胞RNA图谱探索了10个ONB肿瘤和1个嗅黏膜样本中的细胞成分。我们通过在恶性上皮细胞中识别出5种独特的表达程序展示了肿瘤内的异质性。根据不同的基因表达模式建立了一种独特的ONB三分类系统(神经型、基底型、间充质型)。阐明了将实体瘤分类为未表征亚型的生物标志物。根据代表三种肿瘤类型的分子特征,可以谨慎推断对某些化疗方案的不同反应,从而有助于精准化疗。我们还分析了肿瘤微环境(TME)的亚群以及TME内不同细胞类型之间的相互作用。免疫抑制性肿瘤相关巨噬细胞的相对丰度表明靶向巨噬细胞的免疫疗法具有潜在益处。

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