通过单细胞 RNA 测序鉴定喉鳞状细胞癌中癌症干细胞的特征

Yanguo Li, Chen Lin, Yidian Chu, Zhengyu Wei, Qi Ding, Shanshan Gu, Hongxia Deng, Qi Liao, Zhisen Shen
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摘要

癌症干细胞(CSCs)是肿瘤微环境(TME)中的一个关键因素,驱动着癌症的发生和发展。然而,如何识别喉鳞状细胞癌(LSCC)中的癌干细胞及其潜在的分子机制仍然是一项艰巨的挑战。我们采用单细胞RNA测序法对3名LSCC患者的匹配原发肿瘤组织、癌旁组织和局部淋巴结进行了检测。我们划分出了两个不同的干细胞群,它们源于上皮细胞群,并分别被验证为CSCs和正常干细胞(NSCs)。与肿瘤组织相比,癌旁组织中有大量的干细胞。CSCs表现出干细胞标记基因如PROM1、ALDH1A1和SOX4的高表达,并增加了肿瘤相关缺氧、Wnt/β-catenin和Notch信号通路的活性。然后,我们探讨了 CSCs 与 TME 细胞之间错综复杂的相互影响,并确定了 TME 中与 CSCs 相关的靶点。我们还发现了八个与LSCC患者预后显著相关的CSCs标记基因。此外,生物信息学分析表明,厄洛替尼、OSI-027 和伊布替尼等药物可选择性地靶向 CSC 特异性表达的基因。总之,我们的研究结果首次在单细胞水平上全面描述了LSCC中CSCs的特性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Characterization of Cancer Stem Cells in Laryngeal Squamous Cell Carcinoma by Single-cell RNA Sequencing.

Cancer stem cells (CSCs) constitute a pivotal element within the tumor microenvironment (TME), driving the initiation and progression of cancer. However, the identification of CSCs and their underlying molecular mechanisms in laryngeal squamous cell carcinoma (LSCC) remains a formidable challenge. Here, we employed single-cell RNA sequencing of matched primary tumor tissues, paracancerous tissues, and local lymph nodes from three LSCC patients to comprehensively characterize the CSCs in LSCC. Two distinct clusters of stem cells originating from epithelial populations were delineated and verified as CSCs and normal stem cells (NSCs), respectively. CSCs were abundant in the paracancerous tissues compared to those in the tumor tissues. CSCs showed high expression of stem cell marker genes such as PROM1, ALDH1A1, and SOX4, and increased the activity of tumor-related hypoxia, Wnt/β-catenin, and Notch signaling pathways. We then explored the intricate crosstalk between CSCs and the TME cells and identified targets within the TME that related with CSCs. We also found eight marker genes of CSCs that were correlated significantly with the prognosis of LSCC patients. Furthermore, bioinformatics analyses showed that drugs such as erlotinib, OSI-027, and ibrutinib selectively targeted the CSC-specifically expressed genes. In conclusion, our results represent the first comprehensive characterization of CSC properties in LSCC at the single-cell level.

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