Wang Wentao, Zhang Dongyuan, Chang Donglei, Li Yupeng, Ren Lei
Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250014, China.
Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250014, China.
Mol Cell Probes. 2023 Feb;67:101897. doi: 10.1016/j.mcp.2023.101897. Epub 2023 Feb 10.
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.
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.
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).
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.
胰腺腺癌（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中起关键作用。本研究旨在探讨甲基化酶调节因子在PAAD预后和免疫微环境中的潜在作用。
利用PubMed和TCGA数据库系统分析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出三个甲基化酶簇，并使用主成分分析（PCA）基于甲基化酶修饰相关差异表达基因获得三个基因簇。进行京都基因与基因组百科全书（KEGG）通路分析和基因本体（GO）生物学过程分析，以探索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PAAD中亚组与免疫浸润之间的关系。
我们系统筛选了PAAD样本中的43个甲基化酶调节因子，鉴定出具有不同临床结局的三个甲基化酶簇，并检测到甲基化酶簇与肿瘤免疫浸润之间存在显著关系。十大突变基因包括TP53、 Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）、肌联蛋白基因（TTN）、粘蛋白16（MUC16）、SMAD4、细胞周期蛋白依赖性激酶抑制剂2a（CDKN2A）、雷诺丁受体亚型1（RYR1）、环指蛋白43（RNF43）、原钙黏蛋白15（PCDH15）和富含AT相互作用结构域的蛋白1A基因（ARID1A）。
本研究构建了一个m6A/m5C/m1A/m7G调节基因，并探索了与甲基化酶修饰相关的基因，这些基因与PAAD患者的预后以及免疫检查点细胞毒性T淋巴细胞相关蛋白4（CTLA4）有关。这些发现可能为PAAD治疗的预后预测指标和免疫治疗策略提供方向。
