Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient's worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis.

中文翻译：

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肿瘤细胞生物多样性驱动肝癌微环境重编程。

肿瘤中的细胞多样性是实体恶性肿瘤治疗失败和致命结果的关键因素。在这里，我们确定了 19 名患者的肝癌生物样本的单细胞转录组图谱。我们发现肿瘤内部和肿瘤之间的恶性细胞以及肿瘤微环境（TME）的不同景观存在不同程度的异质性。引人注目的是，转录组多样性较高的肿瘤与患者较差的总体生存率相关。我们发现肿瘤多样性中缺氧依赖性血管内皮生长因子的表达与 TME 极化之间存在联系。此外，来自异质性较高的肿瘤的 T 细胞表现出较低的溶细胞活性。使用 765 个肝脏肿瘤的大量基因组和转录组图谱发现了一致的结果。我们的研究结果让我们深入了解肝癌的多样化生态系统及其对患者预后的影响。