Liu Xingyu, Chen Jiarui, Li Jiali, Zeng Zihang, Jiang Xueping, Gao Yanping, Huang Zhengrong, Wu Qiuji, Gong Yan, Xie Conghua
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Genet. 2023 Feb 13;14:1032683. doi: 10.3389/fgene.2023.1032683. eCollection 2023.
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. 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. 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 was hypermethylated in all four cancers and silenced in the transcription factor . 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. This study provides an integrated insight into DNA methylation patterns in alcohol-associated cancers and reveals the corresponding features, influences, and potential mechanisms.
近年来，酒精在致癌过程中的作用受到了越来越多的关注。证据表明其对包括表观遗传改变在内的各个方面都有影响。酒精相关癌症背后的DNA甲基化模式尚未完全明确。我们基于Illumina HumanMethylation450 BeadChip研究了四种酒精相关癌症中的异常DNA甲基化模式。确定了差异甲基化的CpG探针与注释基因之间的皮尔逊系数相关性。使用MEME Suite对转录因子基序进行富集和聚类，并构建了一个调控网络。在每种癌症中，都鉴定出了差异甲基化探针（DMP），并进一步研究了172个高甲基化和21个低甲基化的泛癌DMP（PDMP）。研究了受PDMP显著调控的注释基因，并发现它们在癌症转录失调中富集。CpG岛在所有四种癌症中均发生高甲基化，并在转录因子中沉默。33个高甲基化和7个低甲基化的转录因子基序分为五个簇，发挥了各种生物学效应。在四种酒精相关癌症中，鉴定出11个泛癌DMP与临床结局相关，这可能为临床结局预测提供一个潜在的视角。本研究对酒精相关癌症中的DNA甲基化模式提供了综合见解，并揭示了相应的特征、影响和潜在机制。
