Cheng Jianghong, Li Junyang, Jiang Xinjie, Ma Xi, Li Bixuan, Zhai Han, Luo Xianyang, Zhou Yi, Wu Junhua, Zhang Zhiming, Chen Shuai, Wang Yang
Xi'an Key Laboratory of Pathogenic Microorganism and Tumor Immunity, Xi'an Medical University, Xi'an, 710021, China.
Department of Otolaryngology-Head and Neck Surgery, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, 361003, P.R. China.
Mol Med. 2024 Aug 8;30(1):116. doi: 10.1186/s10020-024-00884-x.
CD74 is ectopically expressed in many tumors and can regulate tumor immunity. However, there are many gaps in the study of the prognostic value of CD74 expression and immune infiltration in hepatocellular carcinoma (HCC).
An online tumor database was searched to obtain data on gene/protein expression. Immune infiltration analysis was performed using the Tumor Immune Estimation Resource and Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer databases. Single-cell data were obtained from the Tissue-specific Gene Expression and Regulation, Single-cell Transcriptomes of Tumor Immune Microenvironment and Tumor Immune Single-cell Hub 2 databases.
CD74 was highly expressed in HCC patients. HCC patients with high CD74 expression who consumed alcohol or were negative for hepatitis virus had a better prognosis than patients with low CD74 expression. CD74 was mainly enriched in immune response regulation pathways. Both copy number variations in CD74 and CD74 expression patterns affected the infiltration levels of immune cells. Interestingly, CD74 regulated the differentiation of myeloid cells. CD74 in macrophages and dendritic cells (DCs) forms complex networks with malignant cells and hepatic progenitor cell (HPC)-like cells, respectively. High CD74 expression in HPC-like cells and malignant cells significantly decreased the fraction of C-type lectin domain family 9 A (CLEC9A)-cDC1 DCs and IL-1B macrophages, respectively. Their crosstalk subsequently shaped the tumor microenvironment of HCC, possibly through the CD74-MIF axis. Importantly, patients with high CD74 expression presented higher immune scores and achieved good outcomes after receiving immunotherapy.
High CD74 expression is associated with the abundance of a variety of immune cell types, mediating interactions among tumor and immune cells and shaping the malignant behavior of HCC. In summary, CD74 may be a hallmark for determining the prognosis and immune cell infiltration levels of HCC patients.
CD74在多种肿瘤中异位表达，可调节肿瘤免疫。然而，关于CD74表达及免疫浸润在肝细胞癌（HCC）中的预后价值研究存在诸多空白。
检索在线肿瘤数据库以获取基因/蛋白表达数据。使用肿瘤免疫估计资源和泛癌数据库中免疫治疗多组学综合分析进行免疫浸润分析。单细胞数据来自组织特异性基因表达与调控、肿瘤免疫微环境单细胞转录组和肿瘤免疫单细胞枢纽2数据库。
CD74在HCC患者中高表达。饮酒或肝炎病毒阴性的高CD74表达HCC患者预后优于低CD74表达患者。CD74主要富集于免疫反应调节途径。CD74的拷贝数变异和表达模式均影响免疫细胞浸润水平。有趣的是，CD74调节髓系细胞分化。巨噬细胞和树突状细胞（DC）中的CD74分别与恶性细胞和肝祖细胞（HPC）样细胞形成复杂网络。HPC样细胞和恶性细胞中高CD74表达分别显著降低C型凝集素结构域家族9A（CLEC9A）-cDC1 DC和IL-1B巨噬细胞的比例。它们之间的串扰随后可能通过CD74-MIF轴塑造HCC的肿瘤微环境。重要的是，高CD74表达患者具有更高的免疫评分，接受免疫治疗后预后良好。
高CD74表达与多种免疫细胞类型的丰度相关，介导肿瘤细胞与免疫细胞之间的相互作用并塑造HCC的恶性行为。总之，CD74可能是确定HCC患者预后和免疫细胞浸润水平的一个标志。
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