Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; Key Laboratory of Carcinogenesis, National Health and Family Planning Commission; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China.
Dis Markers. 2022 May 18;2022:4971621. doi: 10.1155/2022/4971621. eCollection 2022.
The heterogeneity of tumor microenvironment (TME) of hepatocellular carcinoma (HCC) may relate to cell-cell interaction event (CCE) dysregulation and would affect therapeutic responses and clinical outcomes. To reveal the differentiation of CCEs in the liver tissue from healthy donors (HD) to HCC, scRNA-seq data of ~62000 cells from HD, paracancerous nontumor tissue (NT), and HCC were analyzed. The microenvironmental CCE landscape was constructed. Dysregulated cell types and changed molecular functions were identified with CCE alterations in HCC. Dysregulated CCEs which function as pivotal roles in tumorigenesis and development of HCC included SPP1-CD44, MIF-TNFRSF14, and VEGFA-NRP1. A CCE-based immune regulatory network was extracted to illustrate the mechanism of TME dysregulation. A prognostic signature based on CCE genes was identified and validated in independent datasets. Our study provided insights into the characteristics of the cross-talk between tumor cells and microenvironment in HCC and established a workflow strategy for CCE analyses based on scRNA-seq data.
肝癌（HCC）肿瘤微环境（TME）的异质性可能与细胞-细胞相互作用事件（CCE）的失调有关，并会影响治疗反应和临床结局。为了揭示从健康供体（HD）到 HCC 的肝组织中 CCE 的分化，分析了约 62000 个细胞的 scRNA-seq 数据，包括 HD、癌旁非肿瘤组织（NT）和 HCC。构建了微环境 CCE 图谱。鉴定了失调的细胞类型和改变的分子功能，以及 HCC 中 CCE 的变化。失调的 CCE 作为 HCC 发生和发展的关键作用，包括 SPP1-CD44、MIF-TNFRSF14 和 VEGFA-NRP1。提取了基于 CCE 的免疫调节网络，以说明 TME 失调的机制。在独立数据集上验证并验证了基于 CCE 基因的预后特征。我们的研究深入了解了 HCC 中肿瘤细胞与微环境之间相互作用的特征，并建立了基于 scRNA-seq 数据的 CCE 分析工作流程策略。
