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Abstract：
BACKGROUND: Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression.
METHODS: Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines.
RESULTS: We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism.
CONCLUSIONS: These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.
METHODS: Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines.
RESULTS: We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism.
CONCLUSIONS: These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.
摘要：
背景：肿瘤相关巨噬细胞（TAM）构成了人类肝细胞癌（HCC）的重要组成部分。本研究旨在探索TAM多样性及其在HCC进展中的作用。
方法：通过整合来自HCC样本的多个10×单细胞转录组数据，并使用共识非负矩阵分解（无监督聚类算法），详细评估了TAM分子亚型和表达程序。这些TAM亚型在HCC中所起的作用通过假性进一步探讨，富集,和细胞间通讯分析。最后,进行了体外实验以验证CD63之间的关系，CD63是一种炎性TAM表达程序标记，和肿瘤细胞系。
结果：我们发现TAMs中的炎症表达程序与HCC细胞有更明显的相互作用，和CD63，作为炎症表达程序的标记基因，与HCC患者的不良预后相关。大量RNA-seq和体外实验证实，较高的TAMCD63表达与HCC细胞的生长以及上皮-间质转化有关。转移,入侵,和脂质代谢的重新编程。
结论：这些分析表明，肝癌中TAM炎性表达程序与恶性肿瘤细胞密切相关，因此，hub基因CD63代表了这种癌症类型治疗干预的理想靶标。
方法：通过整合来自HCC样本的多个10×单细胞转录组数据，并使用共识非负矩阵分解（无监督聚类算法），详细评估了TAM分子亚型和表达程序。这些TAM亚型在HCC中所起的作用通过假性进一步探讨，富集,和细胞间通讯分析。最后,进行了体外实验以验证CD63之间的关系，CD63是一种炎性TAM表达程序标记，和肿瘤细胞系。
结果：我们发现TAMs中的炎症表达程序与HCC细胞有更明显的相互作用，和CD63，作为炎症表达程序的标记基因，与HCC患者的不良预后相关。大量RNA-seq和体外实验证实，较高的TAMCD63表达与HCC细胞的生长以及上皮-间质转化有关。转移,入侵,和脂质代谢的重新编程。
结论：这些分析表明，肝癌中TAM炎性表达程序与恶性肿瘤细胞密切相关，因此，hub基因CD63代表了这种癌症类型治疗干预的理想靶标。
