School of Ocean and Tropical Medicine, The Second Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China.
Liuzhou Key Laboratory of Molecular Diagnosis, Guangxi Health Commission Key Laboratory of Molecular Diagnosis and Application, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.
Pigment Cell Melanoma Res. 2024 Jul;37(4):496-509. doi: 10.1111/pcmr.13170. Epub 2024 Apr 16.
Recent years have seen rising mortality rates linked to cutaneous melanoma (SKCM), despite advances in immunotherapy. Understanding RNA N6-methyladenosine (M6A) significance in SKCM is crucial for prognosis, tumor microenvironment (TME), immune cell presence, and immunotherapy efficacy. We analyzed 23 M6A regulators using SKCM samples from TCGA and GEO databases, identifying three M6A modification patterns linked to TME cell infiltration. Principal component analysis (PCA) yielded an M6A score for individual tumors, utilizing patient gene expression profiles and CNV data from TCGA. M6A modification patterns play a crucial role in SKCM development and progression, influencing tumor attributes such as inflammatory stage, subtype, TME interstitial activity, and genetic mutations. The M6A score independently predicts patient outcomes and correlates with improved response to immunotherapy, validated across anti-PD-1 and anti-PD-L1 therapy cohorts. M6A modifications significantly impact the TME landscape, with the M6A score serving as a predictive marker for immunotherapy response. Integrating M6A-related information into clinical practice could revolutionize SKCM management and treatment strategies.
近年来，尽管免疫疗法取得了进展，但与皮肤黑色素瘤（SKCM）相关的死亡率仍在上升。了解 RNA N6-甲基腺苷（M6A）在 SKCM 中的意义对于预后、肿瘤微环境（TME）、免疫细胞存在和免疫疗法疗效至关重要。我们使用 TCGA 和 GEO 数据库中的 SKCM 样本分析了 23 个 M6A 调节剂，确定了与 TME 细胞浸润相关的三种 M6A 修饰模式。主成分分析（PCA）利用 TCGA 中的患者基因表达谱和 CNV 数据为每个肿瘤生成了一个 M6A 评分。M6A 修饰模式在 SKCM 的发生和发展中起着关键作用，影响肿瘤的特征，如炎症阶段、亚型、TME 间质活性和遗传突变。M6A 评分独立预测患者的预后，并与对免疫疗法的改善反应相关，在抗 PD-1 和抗 PD-L1 治疗队列中得到验证。M6A 修饰显著影响 TME 景观，M6A 评分是免疫疗法反应的预测标志物。将 M6A 相关信息整合到临床实践中可能会彻底改变 SKCM 的管理和治疗策略。
