Department of General Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Key Laboratory of Bio-inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2022 Oct 24;13:991797. doi: 10.3389/fimmu.2022.991797. eCollection 2022.
Metastatic skin cutaneous melanoma (SKCM) is a common malignancy that accounts for low morbidity but high mortality of skin cancer. SKCM is characterized by high lymphocytic infiltration, whereas the states of infiltrated cells are variable in patients leading to a heterogeneous prognosis and hindering appropriate clinical decisions. It is therefore urgent to identify markers associated with lymphocytic infiltration, cellular conditions, and the prognosis of SKCM. In this study, we report that CEBPB, a transcriptional factor, is mainly expressed in macrophages in metastatic SKCM and associated with an active tumor immune environment and a favorable prognosis through integrated analysis of single-cell and bulk RNA-seq datasets. High CEBPB expression is significantly associated with active inflammation and immune response pathways in both macrophages and bulk SKCM tumor tissues. A signature based on CEBPB-associated genes that are specifically expressed in macrophages could robustly and prognostically separate different metastatic SKCM patients. In addition, the associations between the metastatic SKCM tumor signature and microenvironment with respect to T-cell recruitment and state, inflammation response, angiogenesis, and so on were also determined. In conclusion, we present here the first report on CEBPB in tumor immune environment and prognosis regulation in metastatic SKCM and construct a reliable signature, which should provide a useful biomarker for stratification of the patient's prognosis and therapeutic selection.
转移性皮肤黑色素瘤(SKCM)是一种常见的恶性肿瘤,其发病率低,但皮肤癌死亡率高。SKCM 的特征是淋巴细胞浸润程度高,而患者浸润细胞的状态存在差异,导致预后异质性,从而影响临床决策。因此,迫切需要识别与淋巴细胞浸润、细胞状态和 SKCM 预后相关的标志物。在本研究中,我们通过单细胞和批量 RNA-seq 数据集的综合分析报告,转录因子 CEBPB 主要在转移性 SKCM 的巨噬细胞中表达,与活跃的肿瘤免疫环境和良好的预后相关。高 CEBPB 表达与巨噬细胞和 SKCM 肿瘤组织中的活跃炎症和免疫反应途径显著相关。基于巨噬细胞中特异性表达的与 CEBPB 相关的基因的特征,可以可靠地预测不同转移性 SKCM 患者的预后。此外,还确定了转移性 SKCM 肿瘤特征与微环境之间的关联,包括 T 细胞募集和状态、炎症反应、血管生成等。总之,我们首次报道了 CEBPB 在转移性 SKCM 的肿瘤免疫环境和预后调控中的作用,并构建了一个可靠的特征,该特征应该为患者的预后分层和治疗选择提供有用的生物标志物。