The role of tobacco in carcinogenesis has received increasing attention across a number of disciplines in recent years. Accumulating evidences reveal that tobacco consumption affects various epigenetic modifications, especially DNA methylation. However, the genetic modifications of methylation patterns involved in tobacco-attributable cancers remain poorly understood. In this manuscript, aberrant DNA methylation patterns were investigated in 9 tobacco-attributable cancers. Differential methylated probes (DMPs) were identified in each cancer type and a total of 2,392 hyper- and 736 hypomethylated pan-cancer DMPs (PDMPs) were screened out for further analysis. PDMP-associated genes were mostly enriched in metabolism-associated pathways, suggesting the potential roles of methylation alternation in reprogramming cancer cell metabolism. Hypomethylated PDMPs cg12422154, cg02772121 and cg06051311 constituted an enhancer region, significantly downregulating TRIM15, TRIM26 and RPP21, which serve as epigenetically therapeutic biomarkers. Forty-three hypermethylated and 13 hypomethylated transcription factor motifs were clustered into 6 groups, and exhibited various biological functions. Forty-nine PDMPs were reported to be associated with prognosis, providing effective tools to predict clinical outcomes. In summary, our studies revealed the characteristics, influences and potential mechanisms of DNA methylation patterns of tobacco-attributable cancer.

近年来，烟草在致癌作用中的作用越来越受到许多学科的关注。越来越多的证据表明，烟草消费会影响各种表观遗传修饰，尤其是 DNA 甲基化。然而，与烟草相关癌症相关的甲基化模式的遗传修饰仍然知之甚少。在这份手稿中，研究了 9 种可归因于烟草的癌症中的异常 DNA 甲基化模式。在每种癌症类型中鉴定出差异甲基化探针 (DMP)，并筛选出总共 2,392 个高甲基化和 736 个低甲基化泛癌 DMP (PDMP) 以进行进一步分析。PDMP 相关基因大多富含代谢相关通路，表明甲基化改变在重编程癌细胞代谢中的潜在作用。低甲基化的 PDMPs cg12422154、cg02772121 和 cg06051311 构成一个增强子区域，显着下调 TRIM15、TRIM26 和 RPP21，它们作为表观遗传治疗生物标志物。43 个高甲基化和 13 个低甲基化转录因子基序被分为 6 组，并表现出各种生物学功能。据报道，49 种 PDMP 与预后相关，为预测临床结果提供了有效的工具。总之，我们的研究揭示了烟草引起的癌症的 DNA 甲基化模式的特征、影响和潜在机制。43 个高甲基化和 13 个低甲基化转录因子基序被分为 6 组，并表现出各种生物学功能。据报道，49 种 PDMP 与预后相关，为预测临床结果提供了有效的工具。总之，我们的研究揭示了烟草引起的癌症的 DNA 甲基化模式的特征、影响和潜在机制。43 个高甲基化和 13 个低甲基化转录因子基序被分为 6 组，并表现出各种生物学功能。据报道，49 种 PDMP 与预后相关，为预测临床结果提供了有效的工具。总之，我们的研究揭示了烟草引起的癌症的 DNA 甲基化模式的特征、影响和潜在机制。