DataSheet1_Integrated analysis reveals common DNA methylation patterns of alcohol-associated cancers: A pan-cancer analysis.docx

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.

研究背景：近年来，酒精在肿瘤发生过程中的作用愈发受到学界关注。已有研究证实，酒精可对表观遗传修饰改变等多个生物学层面产生影响，但酒精相关癌症背后的DNA甲基化调控模式尚未完全阐明。
研究方法：本研究基于Illumina HumanMethylation450 微珠芯片（Illumina HumanMethylation450 BeadChip），对4种酒精相关癌症的异常DNA甲基化模式进行分析。通过计算差异甲基化CpG探针与注释基因间的皮尔逊相关系数，筛选得到二者的显著关联。利用MEME套件（MEME Suite）对转录因子基序进行富集分析与聚类，并构建调控网络。
研究结果：在每种癌症样本中均鉴定出差异甲基化探针（differential methylated probes, DMPs），其中172个高甲基化、21个低甲基化的泛癌差异甲基化探针（pan-cancer differential methylated probes, PDMPs）被纳入后续深入研究。对受PDMPs调控的注释基因进行富集分析，发现其显著富集于癌症转录失调通路。位于chr19:58220189–58220517的CpG岛在4种癌症中均呈现高甲基化状态，并可沉默转录因子ZNF154的转录。经聚类分为5组的33个高甲基化与7个低甲基化转录因子基序，可介导多种生物学效应。此外，本研究鉴定出11个泛癌差异甲基化探针与4种酒精相关癌症的临床预后显著相关，可为临床预后预测提供潜在的研究方向。
研究结论：本研究对酒精相关癌症的DNA甲基化模式进行了系统性整合分析，揭示了其相关特征、生物学影响及潜在调控机制。