Mazza Tommaso, Copetti Massimiliano, Capocefalo Daniele, Fusilli Caterina, Biagini Tommaso, Carella Massimo, De Bonis Antonio, Mastrodonato Nicola, Piepoli Ada, Pazienza Valerio, Maiello Evaristo, di Mola Fabio Francesco, di Sebastiano Pierluigi, Andriulli Angelo, Tavano Francesca
Unit of Bioinformatics, Research Hospital, San Giovanni Rotondo 71013, Italy.
Unit of Biostatistics, Research Hospital, San Giovanni Rotondo 71013, Italy.
Oncotarget. 2017 Oct 31;8(62):105320-105339. doi: 10.18632/oncotarget.22184. eCollection 2017 Dec 1.
MiRNA expression abnormalities in adenocarcinoma arising from pancreatic ductal system (PDAC) and Vater's papilla (PVAC) could be associated with distinctive pathologic features and clinical cancer behaviours. Our previous miRNA expression profiling data on PDAC (n=9) and PVAC (n=4) were revaluated to define differences/similarities in miRNA expression patterns. Afterwards, in order to uncover target genes and core signalling pathways regulated by specific miRNAs in these two tumour entities, miRNA interaction networks were wired for each tumour entity, and experimentally validated target genes underwent pathways enrichment analysis. One hundred and one miRNAs were altered, mainly over-expressed, in PDAC samples. Twenty-six miRNAs were deregulated in PVAC samples, where more miRNAs were down-expressed in tumours compared to normal tissues. Four miRNAs were significantly altered in both subgroups of patients, while 27 miRNAs were differentially expressed between PDAC and PVAC. Although miRNA interaction networks were more complex and dense in PDAC than in PVAC, pathways enrichment analysis uncovered a functional overlapping between PDAC and PVAC. However, shared signalling events were influenced by different miRNA and/or genes in the two tumour entities. Overall, specific miRNA expression patterns were involved in the regulation of a limited core signalling pathways in the biology landscape of PDAC and PVAC.
源自胰腺导管系统(PDAC)和 Vater 乳头(PVAC)的腺癌中的 miRNA 表达异常可能与独特的病理特征和临床癌症行为相关。我们之前关于 PDAC(n = 9)和 PVAC(n = 4)的 miRNA 表达谱数据被重新评估,以确定 miRNA 表达模式中的差异/相似性。之后,为了揭示这两种肿瘤实体中特定 miRNA 调控的靶基因和核心信号通路,针对每个肿瘤实体构建了 miRNA 相互作用网络,并对实验验证的靶基因进行了通路富集分析。在 PDAC 样本中,有 101 种 miRNA 发生改变,主要是过度表达。在 PVAC 样本中有 26 种 miRNA 失调,与正常组织相比,肿瘤中更多的 miRNA 表达下调。在两组患者中,有 4 种 miRNA 显著改变,而在 PDAC 和 PVAC 之间有 27 种 miRNA 差异表达。尽管 PDAC 中的 miRNA 相互作用网络比 PVAC 更复杂和密集,但通路富集分析揭示了 PDAC 和 PVAC 之间的功能重叠。然而,两个肿瘤实体中共享的信号事件受不同的 miRNA 和/或基因影响。总体而言,特定的 miRNA 表达模式参与了 PDAC 和 PVAC 生物学景观中有限的核心信号通路的调控。