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Abstract：
Objective: DNA methylation is an essential epigenetic marker governed by DNA methyltransferases (DNMTs), which can influence cancer onset and progression. However, few studies have provided an integrated analysis of the relevance of DNMT family genes to cell stemness, the tumor microenvironment (TME), and immunotherapy biomarkers across diverse cancers. Methods: This study investigated the impact of five DNMTs on transcriptional profiles, prognosis, and their association with Ki67 expression, epithelial-mesenchymal transition signatures, stemness scores, the TME, and immunological markers across 31 cancer types from recognized public databases. Results: The results indicated that DNMT1/DNMT3B/DNMT3A expression increased, whereas TRDMT1/DNMT3L expression decreased in most cancer types. DNMT family genes were identified as prognostic risk factors for numerous cancers, as well as being prominently associated with immune, stromal, and ESTIMATE scores, as well as with immune-infiltrating cell levels. Expression of the well-known immune checkpoints, PDCD1 and CILA4, was noticeably related to DNMT1/DNMT3A/DNMT3B expression. Finally, we validated the role of DNMT1 in MCF-7 and HepG2-C3A cell lines through its knockdown, whereafter a decrease in cell proliferation and migration ability in vitro was observed. Conclusion: Our study comprehensively expounded that DNMT family genes not only behave as promising prognostic factors but also have the potential to serve as therapeutic targets in cancer immunotherapy for various types of cancer.
摘要：
目的:DNA甲基化是DNA甲基转移酶(DNMTs)调控的重要表观遗传标记,会影响癌症的发病和进展。然而,很少有研究对DNMT家族基因与细胞干性的相关性进行了综合分析，肿瘤微环境（TME），和免疫疗法生物标志物在不同的癌症。方法：本研究调查了五种DNMT对转录谱的影响，预后,以及它们与Ki67表达的关联，上皮-间质转化特征，stemness分数,TME,以及来自公认公共数据库的31种癌症类型的免疫学标记。结果:DNMT1/DNMT3B/DNMT3A表达增加,而TRDMT1/DNMT3L在大多数癌症类型中表达降低。DNMT家族基因被确定为许多癌症的预后危险因素。以及与免疫显著相关，基质,和估计分数，以及免疫浸润细胞水平。众所周知的免疫检查点的表达，PDCD1和CILA4与DNMT1/DNMT3A/DNMT3B表达显著相关。最后,我们验证了DNMT1在MCF-7和HepG2-C3A细胞系中的作用，此后观察到体外细胞增殖和迁移能力的降低。结论：我们的研究全面阐述了DNMT家族基因不仅是有希望的预后因素，而且有可能成为各种类型癌症的癌症免疫治疗的治疗靶标。
