Background

Pancreatic adenocarcinoma (PAAD) is a malignant tumor with a high mortality rate. Methylation modifications acted a crucial role to affect cancer progression. The current study aimed to explore the potential role of methylase regulators in PAAD prognosis and immune microenvironment.

Methods

PubMed and TCGA databases were used to systematically analyze methylase regulators in PAAD. We identified three methylase clusters based on RNA methylase transcriptome data and obtained three gene clusters based on methylase modification-related differently expressed genes using principal component analysis (PCA) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) biological processes were performed to explore the processes enriched in the different subgroups and single sample gene-set enrichment analysis (ssGSEA) was used to analyze the relationship between subgroups and immune infiltration in PAAD.

Results

We systematically screened 43 methylase regulators in PAAD samples and identified three methylase clusters with different clinical outcomes, as well as detected a significant relationship between methylase clusters and tumor immune infiltration. The top ten mutated genes include TP53, Kirsten rat sarcoma viral oncogene homolog (KRAS), titin gene (TTN), mucin 16 (MUC16), SMAD4, cyclin-dependent kinase inhibitor 2a (CDKN2A), Ryanodine receptor isoform-1 (RYR1), ring finger 43 (RNF43), protocadherin-15 (PCDH15), and AT-rich interacting domain-containing protein 1 A gene (ARID1A).

Conclusion

The current study constructed an m6A/m5C/m1A/m7G modulator genes and explored methylase modification-related genes, which were related to the prognosis of PAAD patients and the immune checkpoint point cytotoxic T-lymphocyte associated protein 4 (CTLA4). These findings may provide prognostic predictors and direction for immunotherapy strategies for the treatment of PAAD.

中文翻译：

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与胰腺癌预后和免疫特征相关的甲基转移酶修饰基因的鉴定

背景

胰腺癌（PAAD）是一种死亡率很高的恶性肿瘤。甲基化修饰在影响癌症进展方面起着至关重要的作用。目前的研究旨在探讨甲基化酶调节剂在 PAAD 预后和免疫微环境中的潜在作用。

方法

PubMed 和 TCGA 数据库被用来系统地分析 PAAD 中的甲基化酶调节因子。我们基于 RNA 甲基化酶转录组数据鉴定了三个甲基化酶簇，并使用主成分分析 (PCA) 分析获得了三个基于甲基化酶修饰相关差异表达基因的基因簇。进行京都基因与基因组百科全书（KEGG）通路分析和基因本体论（GO）生物过程以探索在不同亚组中富集的过程，并使用单样本基因集富集分析（ssGSEA）分析亚组与基因之间的关系。 PAAD 中的免疫浸润。

结果

我们系统地筛选了 PAAD 样本中的 43 个甲基化酶调节剂，并鉴定了三个具有不同临床结果的甲基化酶簇，并检测到甲基化酶簇与肿瘤免疫浸润之间的显着关系。前十位突变基因包括TP53、Kirsten大鼠肉瘤病毒癌基因同系物（KRAS）、titin基因（TTN）、粘蛋白16（MUC16）、SMAD4、细胞周期蛋白依赖性激酶抑制剂2a（CDKN2A）、Ryanodine receptor isoform-1（RYR1） 、无名指 43 (RNF43)、protocadherin-15 (PCDH15) 和富含 AT 相互作用结构域的蛋白质 1 A 基因 (ARID1A)。

结论

本研究构建了一个m6A/m5C/m1A/m7G调节基因，探索了与PAAD患者预后相关的甲基化酶修饰相关基因和免疫检查点细胞毒性T淋巴细胞相关蛋白4（CTLA4）。这些发现可能为治疗 PAAD 的免疫治疗策略提供预后预测指标和方向。