The Role of COQ10B in Tumor Progression and Its Association with Immune Escape in Esophageal Squamous Cell Carcinoma: A Multi-Omics and Functional Analysis

Leiyu Cao,* Xingfang Wei,* Yu Wei, Xiaoli Ma, Yan Gao, Chengcheng Qu, Wen Yi, Kalima Muhetaer, Li Zhang Cadre Healthcare Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Zhang, Cadre Healthcare Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Tel +86 18799131188, Email zhanglixinjiang@hotmail.comPurpose: This study aims to investigate the role of coenzyme Q10B (COQ10B) in esophageal squamous cell carcinoma (ESCC) and elucidate its potential mechanisms in regulating the tumor immune microenvironment.Patients and Methods: This study integrates bioinformatics, in vitro cell experiments, and in vivo animal models. First, the TCGA and GEO databases were used to analyze correlations between COQ10B expression and ESCC prognosis, signaling pathways, and immune cell infiltration, and single-cell sequencing data were combined to establish its cellular expression profile. Second, TE-1 cells were lentivirally transfected to overexpress COQ10B, and colony formation, EdU, scratch, and Transwell assays were conducted to assess the effects on proliferation, migration, and invasion. Finally, a subcutaneous xenograft model in C57BL/6 mice evaluated COQ10B overexpression and PI3K inhibitor (LY294002) effects on tumor growth, PD-L1 expression, PI3K/AKT/HIF-1A pathway, and immune cell (CD4+ T cells, M2 macrophages) infiltration via Western blotting and flow cytometry.Results: Bioinformatics showed that COQ10B was highly expressed in ESCC and was significantly associated with poor prognosis. Its expression positively correlated with the PI3K-AKT and HIF1 pathways, cancer stem cell genes, and macrophage infiltration. In vitro, COQ10B overexpression enhanced ESCC cell proliferation, migration, and invasion. In vivo, it promoted tumor growth, upregulated PD-L1, p-PI3K, p-AKT, and HIF-1A, reduced CD4+ T cells, and increased M2 macrophages. The PI3K inhibitor LY294002 reversed these pro-tumor and immunosuppressive effects.Conclusion: High COQ10B expression is closely associated with ESCC progression and poor prognosis. These malignant biological behaviors and the associated immunosuppressive tumor microenvironment are potentially mediated via the activation of the PI3K/AKT/HIF-1A signaling pathway.Keywords: esophageal squamous cell carcinoma, COQ10B, PI3K/AKT/HIF-1A, M2 macrophages, tumor microenvironment, PI3K inhibitor