喉鳞状细胞癌中聚集性重塑肿瘤微环境：来自单细胞转录组学的见解

Comparative and Functional Genomics Pub Date : 2026-03-24 DOI:10.1155/ijog/3789337

Hui-min Xu, Ke-xin Ma, Shu-zheng Wang, Hao Wu, Hao-sheng Ni

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引用次数: 0

摘要

肿瘤微环境（tumor microenvironment， TME）在喉鳞癌（LSCC）的发生发展中起着至关重要的作用。然而，吞噬重塑TME的机制尚不清楚。材料与方法从TCGA和GEO数据库中获取LSCC单细胞RNA测序（scRNA-seq）和整体RNA测序（bulk RNA-seq）数据。Seurat和Monocle2包用于细胞聚类和伪时间轨迹分析。使用SCENIC包预测关键转录因子。CellChat软件包用于评估细胞间通信，GSVA方法用于计算大量RNA-seq数据集的签名分数。通过生存分析评估聚集相关亚群的临床意义。免疫荧光染色检测肿瘤组织中TUBA1B的表达及B细胞和T细胞的浸润情况。结果LSCC TME主要由上皮细胞、T/B淋巴细胞和骨髓细胞组成。恶性上皮细胞的TUBA1B + MaligEpi亚群具有最高水平的干性，并与不良预后有关。B细胞的TUBA1B +亚群显示功能受损，而VIM +亚群能够呈递抗原。巨噬细胞的HSP90AA1+亚群表现出高炎症活性，并与TNF/NF-κB信号传导有关。细胞通讯分析显示VIM+和TUBA1C +恶性上皮细胞与CD8+ T细胞相互作用强。这可能是抑制免疫系统的一种方式。TUBA1B在几种类型的癌症中也高表达，并与不良预后有关。免疫荧光证实，B细胞和T细胞免疫浸润伴高表达TUBA1B。结论巨噬是LSCC TME重构的关键驱动因素，TUBA1B是一种有前景的预后生物标志物和潜在的治疗靶点。

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Aggrephagy Reshapes Tumor Microenvironment in Laryngeal Squamous Cell Carcinoma: Insights From Single-Cell Transcriptomics

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Aggrephagy Reshapes Tumor Microenvironment in Laryngeal Squamous Cell Carcinoma: Insights From Single-Cell Transcriptomics

Background

The tumor microenvironment (TME) plays a crucial role in the development and progression of laryngeal squamous cell carcinoma (LSCC). However, the mechanisms by which aggrephagy reshapes the TME remain unclear.

Materials and Methods

Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data of LSCC were obtained from the TCGA and GEO databases. Seurat and Monocle2 packages were employed for cell clustering and pseudotime trajectory analysis. SCENIC package was used to predict key transcription factors. The CellChat package was used to evaluate intercellular communication, and the GSVA method was applied to calculate signature scores across bulk RNA-seq datasets. The clinical significance of aggrephagy-associated subpopulations was assessed through survival analysis. Immunofluorescence staining was performed to evaluate TUBA1B expression and the infiltration of B cells and T cells in tumor tissues.

Results

The LSCC TME was mostly made up of epithelial cells, T/B lymphocytes, and myeloid cells. The TUBA1B + MaligEpi subpopulation of malignant epithelial cells had the highest level of stemness and was linked to a poor prognosis. The TUBA1B + subset of B cells showed impaired function, while the VIM + subset was able to present antigens. The HSP90AA1+ subset of macrophages demonstrated high inflammatory activity and was linked to TNF/NF-κB signaling. Cell communication analysis showed that VIM+ and TUBA1C + malignant epithelial cells and CD8+ T cells interacted strongly with each other. This could be a way for the immune system to be suppressed. TUBA1B was also highly expressed in several types of cancer and was linked to poor prognosis. B cell and T cell immune infiltration was accompanied by high TUBA1B expression, as confirmed by immunofluorescence.