背景：近年来，酒精在癌症发生中的作用受到越来越多的关注。证据表明，它对多个方面产生影响，包括表观遗传学改变。酒精相关癌症的DNA甲基化模式尚未完全理解。 方法：我们基于Illumina HumanMethylation450 BeadChip，调查了四种酒精相关癌症中的异常DNA甲基化模式。鉴定了差异甲基化的CpG探针与注释基因之间的皮尔逊系数相关性。使用MEME Suite进行转录因子基序富集和聚类，并构建了一个调控网络。 结果：在每种癌症中，都鉴定出了差异甲基化的探针，并进一步检查了172个高甲基化和21个低甲基化的全癌症DMPs。调节PDMPs的显著注释基因进行了调查，并且在癌症中的转录调节失常中进行了富集。 CpG岛chr19：58220189-58220517在所有四种癌症中均高甲基化，并在转录因子ZNF154中沉默。被分为五个簇的33个高甲基化和七个低甲基化的转录因子基序具有各种生物学效应。鉴定了11个全癌症DMPs与四种酒精相关癌症的临床结果相关联，这可能为临床结果预测提供了潜在的视角。 结论：本研究提供了对酒精相关癌症中DNA甲基化模式的综合了解，并揭示了相应的特征、影响和潜在机制。版权所有©2023 Liu、Chen、Li、Zeng、Jiang、Gao、Huang、Wu、Gong和Xie。

Background: The role of alcohol in carcinogenesis has received increasing attention in recent years. Evidence shows its impacts on various aspects, including epigenetics alteration. The DNA methylation patterns underlying alcohol-associated cancers are not fully understood. Methods: We investigated the aberrant DNA methylation patterns in four alcohol-associated cancers based on the Illumina HumanMethylation450 BeadChip. Pearson coefficient correlations were identified between differential methylated CpG probes and annotated genes. Transcriptional factor motifs were enriched and clustered using MEME Suite, and a regulatory network was constructed. Results: In each cancer, differential methylated probes (DMPs) were identified, and 172 hypermethylated and 21 hypomethylated pan-cancer DMPs (PDMPs) were examined further. Annotated genes significantly regulated by PDMPs were investigated and enriched in transcriptional misregulation in cancers. The CpG island chr19:58220189-58220517 was hypermethylated in all four cancers and silenced in the transcription factor ZNF154. Various biological effects were exerted by 33 hypermethylated and seven hypomethylated transcriptional factor motifs grouped into five clusters. Eleven pan-cancer DMPs were identified to be associated with clinical outcomes in the four alcohol-associated cancers, which might provide a potential point of view for clinical outcome prediction. Conclusion: This study provides an integrated insight into DNA methylation patterns in alcohol-associated cancers and reveals the corresponding features, influences, and potential mechanisms.Copyright © 2023 Liu, Chen, Li, Zeng, Jiang, Gao, Huang, Wu, Gong and Xie.