DataSheet_1_Integrated analysis from multi-center studies identities m7G-derived modification pattern and risk stratification system in skin cutaneous melanoma.docx

The m7G modification has been proven to play an important role in RNA post-transcriptional modification and protein translation. However, the potential role of m7G modification patterns in assessing the prognosis of Skin cutaneous melanoma (SKCM) and tumor microenvironment (TME) has not been well studied. In this study, we investigated and finally identified 21 available m7G-related genes. We used hierarchical clustering (K-means) to classify 743 SKCM patients into three m7G-modified subtypes named m7G/gene cluster-A, B, C. We found that both m7G cluster B and gene cluster B exhibited higher prognosis and higher immune cell infiltration in TME compared to other subtypes. EIF4E3 and IFIT5, two m7G related genes, were both markedly elevated in Cluster B. Then, we constructed an m7G score system utilizing principal component analysis (PCA) in order to evaluate the patients' prognosis. High m7G score subtype was associated with better survival prognosis and active immune response. Overall, this article revealed that m7G modification patterns were involved in the development of the tumor microenvironment. Evaluating patients' m7G modification patterns will enhance our understanding of TME characteristics and help to guide personal treatment in clinics in the future.

7-甲基鸟苷（m7G）修饰已被证实可在RNA转录后修饰及蛋白质翻译过程中发挥关键调控作用。然而，m7G修饰模式在评估皮肤黑色素瘤（Skin cutaneous melanoma, SKCM）患者预后及肿瘤微环境（tumor microenvironment, TME）特征方面的潜在价值尚未得到充分探究。本研究首先筛选并最终纳入21个与m7G修饰相关的基因。我们采用层次聚类（K-means）算法，将743例皮肤黑色素瘤患者划分为3个m7G修饰亚型，分别命名为m7G/基因簇A、B、C。分析结果显示，相较于其余两个亚型，m7G簇B与基因簇B均呈现出更优的生存预后，且肿瘤微环境中免疫细胞浸润水平更高。进一步的基因表达分析发现，簇B中两个m7G相关基因EIF4E3与IFIT5的表达量均显著上调。随后，本研究借助主成分分析（principal component analysis, PCA）构建了m7G评分系统，用于量化评估患者的预后风险。结果表明，高m7G评分亚型与更好的生存结局及更活跃的抗肿瘤免疫应答显著相关。综上，本研究揭示m7G修饰模式参与肿瘤微环境的重塑与调控。对患者的m7G修饰模式进行精准评估，有助于深化我们对肿瘤微环境特征的认知，并可为未来临床个体化治疗方案的制定提供理论指导。