N⁶-甲基腺苷(N⁶-methyladenosine, m⁶A)修饰是真核生物信使 RNA中最丰富的表观遗传修饰,其失调会导致mRNA异常生物学行为如翻译和降解紊乱,从而调控肿瘤发生发展。近期研究表明m⁶A在免疫调控过程中可发挥重要作用,其不仅可调节免疫细胞的活化,还在肿瘤微环境中免疫应答发挥重要调控作用,从而影响免疫治疗效果。越来越多的证据表明m⁶A修饰可能是肿瘤免疫治疗的重要潜在干预靶点。本文阐述了免疫细胞中m⁶A修饰调控及其在肿瘤免疫微环境中相关调节作用,并进一步探讨了靶向m⁶A调控蛋白在肿瘤免疫治疗中的干预策略及潜在治疗价值。

N⁶-methyladenosine (m⁶A) modification is the most abundant epigenetic modification in eukaryotic messenger RNA (messenger RNA). Its dysregulation drives abnormal transcription and translation processes, which promotes the occurrence and development of tumors. Studies have shown that m⁶A modification can regulate the activation of immune cells and their infiltration into the tumor microenvironment (TME), which may affect the efficiency of immunotherapy. Therefore, m⁶A modification may be a potential target for tumor immunotherapy. This paper describes the modification of m⁶A in immune cells and the antitumor immune response associated with TME, and explores the potential therapeutic value of targeting m⁶A regulators in tumor immunotherapy.

目的 使用TCGA数据库,探索DNA甲基化位点对肺腺癌的预后影响。方法 使用TCGA数据库,获取肺腺癌病人癌和癌旁组织甲基化表达数据、基因表达数据及临床数据;将人群分为探索组和验证组,使用LASSO在探索人群中筛选对肺腺癌预后有影响的甲基化位点;受试者工作特征曲线用于评估甲基化位点预测效果,并进一步在验证人群中验证。结果 在TCGA数据库中筛选出158个癌和癌旁组织差异表达且与所在基因mRNA表达显著相关的甲基化位点,经LASSO回归分析,cg19378330与肺腺癌预后相关。甲基化位点水平高于中位数的患者,归入高风险组,甲基化位点水平低于中位数的为低风险组。结果发现与低风险组相比,高风险组的死亡风险比低风险组增加了38%(OR=1.38,95% CI=1.16～2.69)。在探索阶段人群中其曲线下面积为0.80(95% CI=0.73～0.88),灵敏度为86.2%。验证人群中也表现出类似结果。结论 甲基化位点cg19378330与肺腺癌具有较显著的关联性,且可以对肺腺癌的风险进行有效的预测。

Objective Using the TCGA database to explore the prognostic effects of DNA methylation sites on lung adenocarcinoma. Methods TCGA database was used to collecting DNA methylation data, gene expression data and clinical data of lung adenocarcinoma patients. The population were divided into the exploratory group and the validation group. The LASSO regression analysis was used to screen the methylation sites associated with the prognosis of lung adenocarcinoma in the exploratory group. Receiver operating characteristic curve was used to evaluate the prediction effect of the model, and further verified in the validation population. Results A total of 158 methylation sites with differential expression and significant correlation with the mRNA expression of the corresponding gene were screened from the TCGA database. With LASSO regression analysis, the DNA methylation sites associated with prognosis of lung adenocarcinoma were cg19378330. Those patients with levels above the median methylation site were assigned to the high-risk group, while those with levels below the median methylation site were assigned to the low-risk group. Patients' death risk in the high-risk group were 38% higher than those in the low-risk group (OR=1.38, 95%CI=1.16-2.69). The area under the curve was 0.80 (95%CI=0.73-0.88) and the sensitivity was 86.2% in the exploratory stage population.Similar results were seen in the validation population. Conclusions The DNA methylation site cg19378330 was significantly associated withthe prognosisof lung adenocarcinoma, and could effectively predict the risk of lung adenocarcinoma.