卵巢癌（OC）中的肿瘤相关lncRNA受表观遗传修饰开关调节免疫逃逸和化疗抗性。然而，尚未系统阐明其潜在机制和具体靶点。在这里，我们发现甲基化修饰在调控免疫细胞浸润和增强OC对化疗的敏感性方面起到了重要作用，通过调节与免疫相关的lncRNA（irlncRNA），代表肿瘤免疫状态。通过对TCGA数据库的深入分析，我们构建了包含四个甲基化相关lncRNA（mrlncRNA）和irlncRNA的预后风险模型。鉴定到21个与OC患者整体生存（OS）显著相关的mrlncRNA/irlncRNA对。随后，我们选择了四个lncRNA构建了一个预测OS并指示OC免疫浸润的风险签名，并在内部验证集中验证了风险签名的稳定性。风险得分是OC预后的独立预测因子，这通过多因素Cox回归分析和示意图得到了证明。此外，风险分数与CD274、CTLA4、ICOS、LAG3、PDCD1和PDCD1LG2的表达呈负相关，并与CD8+、CD4+和Treg肿瘤浸润免疫细胞呈负相关。此外，高风险分数与顺铂的IC50值较高相关，与明显较差的临床结局相关。接下来，基于lncRNA模型，探索了一个竞争性内源性RNA（ceRNA）网络和一个控制CD8+ T细胞浸润的信号通路，为免疫治疗提供了一个潜在的治疗靶点。总的来说，本研究通过配对mrlncRNA和irlncRNA构建了一个预后模型，并揭示了FTO/RP5-991G20.1/hsa-miR-1976/MEIS1信号通路在调节免疫功能和增强抗癌疗法中的关键作用。© 2023年 BioMed Central Ltd.，Springer Nature的一部分。

Tumor-associated lncRNAs regulated by epigenetic modification switches mediate immune escape and chemoresistance in ovarian cancer (OC). However, the underlying mechanisms and concrete targets have not been systematically elucidated. Here, we discovered that methylation modifications played a significant role in regulating immune cell infiltration and sensitizing OC to chemotherapy by modulating immune-related lncRNAs (irlncRNAs), which represent tumor immune status. Through deep analysis of the TCGA database, a prognostic risk model incorporating four methylation-related lncRNAs (mrlncRNAs) and irlncRNAs was constructed. Twenty-one mrlncRNA/irlncRNA pairs were identified that were significantly related to the overall survival (OS) of OC patients. Subsequently, we selected four lncRNAs to construct a risk signature predictive of OS and indicative of OC immune infiltration, and verified the robustness of the risk signature in an internal validation set. The risk score was an independent prognostic factor for OC prognosis, which was demonstrated via multifactorial Cox regression analysis and nomogram. Moreover, risk scores were negatively related to the expression of CD274, CTLA4, ICOS, LAG3, PDCD1, and PDCD1LG2 and negatively correlated with CD8+, CD4+, and Treg tumor-infiltrating immune cells. In addition, a high-risk score was associated with a higher IC50 value for cisplatin, which was associated with a significantly worse clinical outcome. Next, a competing endogenous RNA (ceRNA) network and a signaling pathway controlling the infiltration of CD8+ T cells were explored based on the lncRNA model, which suggested a potential therapeutic target for immunotherapy. Overall, this study constructed a prognostic model by pairing mrlncRNAs and irlncRNAs and revealed the critical role of the FTO/RP5-991G20.1/hsa-miR-1976/MEIS1 signaling pathway in regulating immune function and enhancing anticancer therapy.© 2023. BioMed Central Ltd., part of Springer Nature.