Wei Jiahui, Wang Ming, Xu Shuiqing, Tusufuhan Paizigul, Wu Yumei
Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing, China.
Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Front Immunol. 2025 May 29;16:1571842. doi: 10.3389/fimmu.2025.1571842. eCollection 2025.
ME1 catalyzes the conversion of malic acid into acetic acid, thereby linking glucose metabolism to the citric acid cycle. In recent years, the role of ME1 in various tumors has only been superficially explored. Therefore, our objective is to analyze the potential functions of ME1 in pan-cancer, with a particular focus on its role in ovarian cancer.
We analyzed the ME1 expression levels in both normal and tumor tissues across various cancer types. CBIOPORTAL was utilized to assess the mutation frequency and specific sites of ME1. Additionally, we examined the correlation between ME1 expression and several factors, including methylation status, tumor mutation burden (TMB), microsatellite instability (MSI), immune regulator genes, immune checkpoints, tumor microenvironment scores, functional enrichment, single-cell analysis, and drug sensitivity. The Estimate Algorithm assessed the correlation between ME1 expression and the tumor immunochemical microenvironment. Small interfering RNA and chronic viruses were utilized to downregulate and upregulate ME1 expression in two ovarian cancer cell lines, respectively, to conduct experiments on cell proliferation and migration.
Our results revealed that ME1 exhibited disorders across various tumors, with the predominant form of genetic mutation identified being a missense mutation. Among the various tumors analyzed, ME1 demonstrated a significant correlation with methylation levels, TMB, MSI, immune checkpoints, immunomodulatory regulatory genes, tumor microenvironment scores, and immune infiltration. Functional enrichment analysis and single-cell analysis indicated that ME1 expression was associated with metabolic regulation, macrophage immune responses, antioxidant defense mechanisms, and the potential tumor microenvironment. The elevated levels of ME1 may be associated with a more favorable response to specific immunotherapy, suggesting that ME1 has potential applications in guiding immunotherapeutic strategies. research results demonstrated that in ovarian cancer cell lines, the knockdown of ME1 inhibited the proliferation and migration of tumor cells. Conversely, the overexpression of ME1 appeared to promote tumor cell proliferation and migration.
ME1, a metabolic-related factor, has the potential to serve as a biomarker for tumor progression and immune infiltration, particularly in ovarian cancer. It may signify a metabolic reprogramming that supplies energy for tumor progression and immunotherapy, offering valuable insights for the development of personalized therapies.
苹果酸酶1（ME1）催化苹果酸转化为乙酸，从而将葡萄糖代谢与柠檬酸循环联系起来。近年来，ME1在各种肿瘤中的作用仅得到了初步探索。因此，我们的目的是分析ME1在泛癌中的潜在功能，尤其关注其在卵巢癌中的作用。
我们分析了多种癌症类型的正常组织和肿瘤组织中ME1的表达水平。利用CBIOPORTAL评估ME1的突变频率和特定位点。此外，我们还研究了ME1表达与多种因素之间的相关性，包括甲基化状态、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、免疫调节基因、免疫检查点、肿瘤微环境评分、功能富集、单细胞分析和药物敏感性。Estimate算法评估了ME1表达与肿瘤免疫化学微环境之间的相关性。分别利用小干扰RNA和慢病毒下调和上调两种卵巢癌细胞系中ME1的表达，以进行细胞增殖和迁移实验。
我们的结果显示，ME1在各种肿瘤中表现出紊乱，鉴定出的主要基因突变形式为错义突变。在分析的各种肿瘤中，ME1与甲基化水平、TMB、MSI、免疫检查点、免疫调节基因、肿瘤微环境评分和免疫浸润显著相关。功能富集分析和单细胞分析表明，ME1表达与代谢调节、巨噬细胞免疫反应、抗氧化防御机制以及潜在的肿瘤微环境有关。ME1水平升高可能与对特定免疫疗法的更有利反应相关，这表明ME1在指导免疫治疗策略方面具有潜在应用价值。研究结果表明，在卵巢癌细胞系中，敲低ME1可抑制肿瘤细胞的增殖和迁移。相反，ME1的过表达似乎促进肿瘤细胞的增殖和迁移。
ME1作为一种与代谢相关的因子，有可能作为肿瘤进展和免疫浸润的生物标志物，尤其是在卵巢癌中。它可能意味着一种为肿瘤进展和免疫治疗提供能量的代谢重编程，为个性化治疗的发展提供有价值的见解。
