[摘 要] 目的：探讨m6A调控因子在宫颈癌预后评估、免疫微环境特征及治疗反应中的作用，构建基于m6A调控因子的预后风险模型，并分析其与免疫浸润、药物敏感性及细胞间通信的关系。方法：基于TCGA和GEO数据库中宫颈鳞癌及腺癌（CESC） 转录组数据，分析22个m6A调控因子的表达与突变情况；采用LASSO?Cox回归构建m6A相关预后风险模型，并依据风险评分将患者分为高、低风险组。利用CIBERSORT和ESTIMATE算法评估两组免疫细胞浸润及微环境特征；通过oncoPredict预测抗肿瘤药物敏感性。整合单细胞转录组数据（E-MTAB-12305），采用CellChat分析细胞间通信网络。结果：共鉴定出12个在宫颈癌中差异表达的m6A调控因子。高风险组患者总生存期缩短（P < 0.05），免疫评分降低，且对紫杉醇、氟尿嘧啶、多柔比星等抗肿瘤药物敏感性较差（IC50较高）。单细胞分析显示宫颈癌组织中细胞间通信网络发生改变，其中T细胞与内皮/上皮细胞间的相互作用可能主要由CCL5?ACKR1和MIF?（CD74 + CXCR4）配体?受体介导。在临床样本中，对关键的m6A调控因子进行mRNA和蛋白水平的验证，结果显示部分调控因子在宫颈癌组织中的表达水平高于正常宫颈组织（P < 0.05）。结论：m6A调控因子特征可有效预测宫颈癌患者预后，其风险评分与肿瘤免疫浸润、药物敏感性及细胞通信密切相关，为宫颈癌的预后分层及个体化治疗提供了新的分子依据。

[Abstract] Objective: To investigate the role of m6A regulators in prognostic evaluation, immune microenvironment characteristics, and treatment response in cervical cancer, to construct a prognostic risk model based on m6A regulators, and to analyze its associations with immune infiltration, drug sensitivity, and intercellular communication. Methods: Transcriptomic data of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) from the TCGA and GEO databases were used to analyze the expression and mutation profiles of 22 m6A regulators. A prognostic risk model was established using LASSO?Cox regression, and patients were stratified into high? and low?risk groups based on risk scores. Immune cell infiltration and microenvironment characteristics were evaluated using CIBERSORT and ESTIMATE algorithms. Antitumor drug sensitivity was predicted using oncoPredict. Single?cell transcriptomic data (E?MTAB?12305) were integrated to analyze intercellular communication networks using CellChat. Results: A total of 12 differentially expressed m6A regulators were identified in cervical cancer. Patients in the high?risk group showed significantly shorter overall survival (P < 0.05), lower immune scores, and reduced sensitivity to antitumor drugs such as paclitaxel, fluorouracil, and doxorubicin, as indicated by higher IC50 values. Single?cell analysis revealed altered intercellular communication networks in cervical cancer tissues, with interactions between T cells and endothelial/epithelial cells mainly mediated by the CCL5?ACKR1 and MIF?(CD74 + CXCR4) ligand?receptor pairs. Validation of key m6A regulators at the mRNA and protein levels in clinical samples showed that most regulators were significantly more highly expressed in cervical cancer tissues than in healthy human cervical tissues. Conclusion: The m6A regulator-based prognostic signature can effectively predict the prognosis of patients with cervical cancer. The risk score is closely associated with tumor immune infiltration, drug sensitivity, and intercellular communication, providing a novel molecular basis for · · 678 [[PAGE_INDEX=10 FILE=37dae296-6188-4ec2-9b39-45b08e05f9a4.pdf]] 蒋本贵, 等. 基于m6A调控因子的预后模型与宫颈癌免疫浸润、药物敏感性及细胞间通信的综合分析prognostic stratification and personalized therapy in cervical cancer.

[基金项目] 宁波市妇科疾病临床研究中心（2024L002）；浙江省医药卫生科技计划项目（2023KY293）