Network-based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer
Network-based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer
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基于网络的 mRNA 和 miRNA 图谱整合揭示了胰腺癌中涉及的新靶基因
DOI：
10.1002/mc.22920
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发表时间：
2018
影响因子：
4.6
通讯作者：
Zhang Yan
中科院分区：
文献类型：
--
作者：
Lin Jie;Wu Yan-Jun;Liang Xing;Ji Meng;Ying Hui-Min;Wang Xin-Yu;Sun Xia;Shao Cheng-Hao;Zhan Li-Xing;Zhang Yan
胰腺癌因其5年生存率低、预后差而被认为是最致命、最具侵袭性的恶性肿瘤。胰腺癌的早期诊断和治疗手段有限，迫切需要了解胰腺癌发生的复杂机制。在这项研究中，我们使用RNA-seq技术研究了10名患者的胰腺癌配对肿瘤和正常胰腺组织中的转录(mRNA和miRNA)谱。发现了1000多个差异表达基因，其中近一半在大多数接受检查的患者中也发现了差异表达。功能富集分析表明，这些基因在多细胞生物和代谢过程、分泌、矿物质运输和细胞间通讯中显著丰富。此外，只发现了24个差异表达的miRNAs，所有这些miRNAs都被报道与胰腺癌有关。此外，还利用多种资源构建了一个完整的miRNA-mRNA相互作用网络。根据疾病相关性得分的计算，白蛋白、ATPase H+/K+交换α多肽和癌胚抗原相关细胞黏附分子1等存在于最大连通子网络中的几个基因被认为是在胰腺癌发生发展中发挥重要作用的新基因。总体而言，我们的数据为进一步了解胰腺肿瘤发生的关键分子机制提供了新的见解。
Pancreatic cancer is regarded as the most fatal and aggressive malignancy cancer due to its low 5‐year survival rate and poor prognosis. The approaches of early diagnosis and treatment are limited, which makes it urgent to identify the complex mechanism of pancreatic oncogenesis. In this study, we used RNA‐seq to investigate the transcriptomic (mRNA and miRNA) profiles of pancreatic cancer in paired tumor and normal pancreatic samples from ten patients. More than 1000 differentially expressed genes were identified, nearly half of which were also found to be differentially expressed in the majority of examined patients. Functional enrichment analysis revealed that these genes were significantly enriched in multicellular organismal and metabolic process, secretion, mineral transport, and intercellular communication. In addition, only 24 differentially expressed miRNAs were found, all of which have been reported to be associated with pancreatic cancer. Furthermore, an integrated miRNA‐mRNA interaction network was generated using multiple resources. Based on the calculation of disease correlation scores developed here, several genes present in the largest connected subnetwork, such as albumin, ATPase H+/K+exchanging alpha polypeptide and carcinoembryonic antigen‐related cell adhesion molecule 1, were considered as novel genes that play important roles in the development of pancreatic cancer. Overall, our data provide new insights into further understanding of key molecular mechanisms underlying pancreatic tumorigenesis.