Among all causes of death, cancer is the most prevalent and is only outpaced by cardiovascular diseases. Molecular theory of carcinogenesis states that apoptosis and proliferation are regulated by groups of tumor suppressors or oncogenes. Transcription factors are example of proteins comprising representatives of both cancer-related groups. Exemplary family of transcription factors which exhibits dualism of function is Activating enhancer-binding Protein 2 (AP-2). Scientific reports concerning their function in carcinogenesis depend on particular family member and/or tumor type which proves the issue to be unsolved. Therefore, the present study examines role of the best-described AP-2 representatives, AP-2α and AP-2γ, through ontological analysis of their target genes and investigation what processes are differentially regulated in 21 cancers using samples deposited in Genomic Data Analysis Center (GDAC) Firehose. Expression data with clinical annotation was collected from TCGA-dedicated repository GDAC Firehose. Transcription factor targets were obtained from Gene Transcription Regulation Database (GTRD), TRANScription FACtor database (TRANSFAC) and Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST). Monocle3 R package was used for global samples profiling while Protein ANalysis THrough Evolutionary Relationships (PANTHER) tool was used to perform gene ontology analysis. With RNA-seq data and Monocle3 or PANTHER tools we outlined differences in many processes and signaling pathways, separating tumor from normal tissues or tumors from each other. Unexpectedly, a number of alterations in basal-like breast cancer were identified that distinguished it from other subtypes, which could bring future clinical benefits. Our findings indicate that while the AP-2α/γ role remains ambiguous, their activity is based on processes that underlie the cancer hallmarks and their expression could have potential in diagnosis of selected tumors.

中文翻译：

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AP-2α和AP-2γ在癌症中的功能基因组学：计算机研究

在所有死亡原因中，癌症是最普遍的，仅在心血管疾病方面胜过。致癌分子理论指出，凋亡和增殖受肿瘤抑制因子或癌基因的调控。转录因子是包含两个癌症相关群体的代表的蛋白质的例子。表现出功能双重性的示例性转录因子家族是激活增强子结合蛋白2（AP-2）。关于其在致癌作用中的功能的科学报道取决于特定的家庭成员和/或肿瘤类型，这证明该问题尚未解决。因此，本研究考察了最能描述AP-2代表AP-2α和AP-2γ的作用，通过对其靶基因的本体分析，并使用基因组数据分析中心（GDAC）Firehose中保存的样本调查21种癌症中哪些过程受到差异调节。具有临床注释的表达数据是从TCGA专用存储库GDAC Firehose收集的。转录因子靶标是从基因转录调控数据库（GTRD），TRANScription FACtor数据库（TRANSFAC）和基于句子的文本挖掘（TRRUST）揭示的转录调控关系中获得的。Monocle3 R软件包用于全局样品分析，而蛋白质分析通过进化关系（PANTHER）工具用于进行基因本体分析。利用RNA序列数据和Monocle3或PANTHER工具，我们概述了许多过程和信号传导途径的差异，将肿瘤与正常组织或彼此分离。出乎意料的是，已发现基底样乳腺癌的许多改变将其与其他亚型区分开来，这可能带来未来的临床益处。我们的发现表明，虽然AP-2α/γ的作用仍然不明确，但它们的活性是基于构成癌症标志物的过程，并且它们的表达可能具有诊断所选肿瘤的潜力。