Department of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, No. 1 Xinmin Road, Changchun, Jilin, 130000, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, No 246, Xuefu Road, Nangang District, Harbin, 150001, Heilongjiang, China.
BMC Cancer. 2024 Nov 27;24(1):1455. doi: 10.1186/s12885-024-13225-2.
Aberrant expression of N3-methylcytidine methyltransferase 2B (METTL2B) has been observed in various human malignancies, including those of the prostate, liver, breasts, and bladder. However, its role in ovarian cancer (OC) remains largely unexplored. This research preliminarily investigated METTL2B expression in OC and elucidated the associated molecular mechanisms.
We utilized three publicly available cancer-related databases (Genotype-Tissue Expression, Gene Expression Omnibus, and The Cancer Genome Atlas) to identify gene signatures in patients with OC and normal individuals with a specific focus on METTL2B. The role of METTL2B in OC was evaluated using patient survival data, and its impact on oncogenic behaviors in both cell and animal models, including growth potential, migration, invasion, and the tumor microenvironment, was examined. This assessment was conducted using bioinformatics tools such as Gene Set Cancer Analysis, GeneMANIA, and Tumor Immune Single-cell Hub 2. Additionally, the association between drug sensitivity and METTL2B expression was analyzed using CellMiner.
METTL2B expression was significantly elevated in OC, highlighting its potential clinical value in the diagnosis and prognosis of OC. Patients with lower METTL2B expression exhibited favorable survival. Furthermore, METTL2B knockdown significantly disrupted oncogenic behaviors in OC cell lines by suppressing the mTOR/AKT signaling pathway. Additionally, bioinformatics-based Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested a close correlation between METTL2B and immune responses.
Our research confirmed the upregulation of METTL2B in OC, suggesting its oncogenic function. However, METTL2B expression was negatively correlated with the infiltration scores of multiple immune cells, including cytotoxic cells and T cells, indicating its complex role in the tumor immune microenvironment. These findings highlight the significant clinical value of METTL2B in the diagnosis and prognosis of OC.
N3-甲基胞苷甲基转移酶 2B（METTL2B）的异常表达已在多种人类恶性肿瘤中观察到，包括前列腺癌、肝癌、乳腺癌和膀胱癌。然而，其在卵巢癌（OC）中的作用在很大程度上仍未得到探索。本研究初步研究了 METTL2B 在 OC 中的表达，并阐明了相关的分子机制。
我们使用了三个公开的癌症相关数据库（基因型组织表达、基因表达综合数据库和癌症基因组图谱）来鉴定 OC 患者和正常个体的基因特征，特别关注 METTL2B。使用患者生存数据评估 METTL2B 在 OC 中的作用，并在细胞和动物模型中研究其对致癌行为的影响，包括生长潜力、迁移、侵袭和肿瘤微环境。使用 Gene Set Cancer Analysis、GeneMANIA 和 Tumor Immune Single-cell Hub 2 等生物信息学工具进行评估。此外，使用 CellMiner 分析药物敏感性与 METTL2B 表达之间的关系。
METTL2B 在 OC 中的表达显著升高，提示其在 OC 的诊断和预后中有潜在的临床价值。METTL2B 表达较低的患者生存状况较好。此外，METTL2B 敲低通过抑制 mTOR/AKT 信号通路显著破坏 OC 细胞系的致癌行为。此外，基于生物信息学的基因本体论和京都基因与基因组百科全书分析表明，METTL2B 与免疫反应密切相关。
我们的研究证实了 METTL2B 在 OC 中的上调，表明其具有致癌功能。然而，METTL2B 表达与多种免疫细胞（包括细胞毒性细胞和 T 细胞）的浸润评分呈负相关，表明其在肿瘤免疫微环境中的作用复杂。这些发现突出了 METTL2B 在 OC 的诊断和预后中的重要临床价值。
