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

IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Molecular and Cellular Probes Pub Date : 2023-02-01 DOI:10.1016/j.mcp.2023.101897
Wentao Wang , Dongyuan Zhang , Donglei Chang , Yupeng Li, Lei Ren
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引用次数: 0

摘要

背景胰腺癌是一种死亡率较高的恶性肿瘤。甲基化修饰在影响癌症进展中起着至关重要的作用。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。方法利用PubMed和TCGA数据库对PAAD中的甲基化酶调节因子进行系统分析。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的不同表达基因的基因簇。采用京都基因和基因组百科全书(KEGG)通路分析和基因本体论(GO)生物学过程来探索不同亚组中富集的过程,并采用单样本基因集富集分析(ssGSEA)来分析PAAD亚组与免疫浸润的关系。结果我们系统地筛选了PAAD样本中的43种甲基化酶调节因子,并鉴定了三个具有不同临床结果的甲基化酶簇,并检测到甲基化酶团与肿瘤免疫浸润之间的显著关系。前十个突变基因包括TP53、Kirsten大鼠肉瘤病毒癌基因同源物(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受体异构体-1(RYR1)、无名指43(RNF43)、原粘附素-15(PCDH15)和富含AT的相互作用结构域的蛋白1A基因(ARID1A)。结论本研究构建了一个m6A/m5C/m1A/m7G调控基因,并探索了与PAAD患者预后和免疫检查点细胞毒性T淋巴细胞相关蛋白4(CTLA4)有关的甲基化酶修饰相关基因。这些发现可能为PAAD的免疫治疗策略提供预后预测因素和方向。
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Identification of methyltransferase modification genes associated with prognosis and immune features of pancreatic adenocarcinoma

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.

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来源期刊
Molecular and Cellular Probes
Molecular and Cellular Probes 生物-生化研究方法
CiteScore
6.80
自引率
0.00%
发文量
52
审稿时长
16 days
期刊介绍: MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.
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