线粒体能量代谢(MEM)的重编程是肿瘤发生和癌症进展的重要标志。目前，尚无研究在食管鳞状细胞癌(ESCC)的肿瘤微环境(TME)中研究MEM，并且尚未确定相关药物靶点。本研究通过使用AUCell R软件包对ESCC单细胞转录组测序数据集GSE145370进行分析，筛选出TME高得分细胞群中的MEM相关基因。利用Monocle推断细胞分化，利用CellChat分析细胞间通信网络。最后，利用15例ESCC患者的互补DNA微阵列分析预后基因的转录水平。在TME的七个细胞群中，共有121个MEM相关基因表达差异显著，并确定了四个高得分细胞群。结果显示，T细胞的MEM状态与巨噬细胞和上皮细胞显著不同，而T细胞与巨噬细胞之间的信号通信最强。这些发现表明，免疫抑制与代谢重编程相关。此外，高得分细胞的标记基因和前10个受体-配体对可能成为重建免疫细胞代谢的新靶点。此外，4-MEM基因风险签名具有较好的整体生存和药物敏感性预测能力。MAP1LC3A、APOE、APPL1和NDUFA是重构TME的潜在新的免疫治疗靶点。最后，利用实时定量PCR验证了APOE和MAP1LC3A的表达。观察到ESCC免疫抑制性TME中的MEM异质性。基于MEM相关基因的预后模型有助于筛选早期治疗患者群体和实现个体化治疗。APOE和MAP1LC3A是基于MEM相关基因开发抗ESCC药物的潜在靶基因。© 2023 作者。

Reprogramming of mitochondrial energy metabolism (MEM) is an important hallmark of tumorigenesis and cancer progression. Currently, there are no studies that have examined MEM in the tumor microenvironment (TME) of esophageal squamous cell carcinoma (ESCC), and relevant drug targets have not yet been identified.The ESCC single-cell transcriptome sequencing dataset, GSE145370, was analyzed, using the AUCell R package to screen for MEM-related genes in high-scoring cell populations. Monocle was used to infer cell differentiation and CellChat to analyze intercellular communication networks. Finally, transcription levels of prognostic genes were analyzed using a complementary DNA microarray from 15 patients with ESCC.A total of 121 MEM-related genes were differentially expressed in seven cell populations in the TME, and four high-scoring cell populations were identified. As a result, the MEM state of T cells is significantly different from that of macrophages and epithelial cells, and signaling communication between T cells and macrophages is the strongest. These findings suggest that immunosuppression is related to metabolic reprogramming. Additionally, marker genes of high-scoring cells and the top10 receptor-ligand pairs may become new targets for rebuilding immune cell metabolism. Furthermore, the 4-MEM gene risk signature had good predictive power for overall survival and drug sensitivity. MAP1LC3A, APOE, APPL1, and NDUFA are novel potential immunotherapeutic targets for remodeling the TME. Finally, teal-time quantitative PCR was used to verify APOE and MAP1LC3A expression.MEM heterogeneity was observed in the immunosupressive TME of ESCC. Prognostic models based on MEM-related genes are helpful for screening early treatment patient groups and realizing personalized treatment. APOE and MAP1LC3A are potential target genes for the development of anti-ESCC drugs based on MEM-related genes.© 2023 The Authors.