Yang Yuemei, Wang Yanfeng, Liu Shizhong, Zhao Xiaoling, Jia Rujing, Xiao Yu, Zhang Ming, Li Xiaoou, Li Ji, Wang Wenze
Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of R&D Technology Center, Beijing Zhicheng Biomedical Technology Co Ltd, Beijing, China.
J Cell Biochem. 2019 May;120(5):7802-7813. doi: 10.1002/jcb.28055. Epub 2018 Nov 28.
Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world for early metastasis, extensive invasion, and poor prognosis with a 5-year survival rate less than 5%. However, the underlying mechanisms are poorly understood. Therefore, it is urgent to explore molecular markers for early diagnosis or therapy target to improve the outcome of PAAD.
We retrieved transcriptome data as well as clinical information from patients with PAAD in The Cancer Genome Altas (TCGA) database. Survival time associated microRNAs (miRNAs) and messenger RNAs (mRNAs) were initially identified, followed by enrichment analysis (Gene Ontology [GO] and pathway). The relationship between survival time associated miRNAs-mRNAs was also investigated to discover putative transcriptional control mechanisms of PAAD. Finally, by consulting the literature and retrieving the database, we found that hsa-miR-495 might have played an important role in PAAD.
In total, 146 miRNAs from 378 miRNAs and 580 mRNA from 17 100 mRNA, including 328 risk mRNA and 252 protective mRNA, were found to be associated with the survival time of PAAD. Eight hundred eighty-eight mRNA-miRNA pairs were related to the survival time of PAAD, involving in 755 mRNAs and 35 miRNAs. We chose 13 miRNAs predicted by target gene in the miRanda database for further research. Among these 13 miRNAs, hsa-miR-495 was identified as a good biomarker. Through GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the significantly enriched pathways involved in focal adhesion, Staphylococcus aureus infection, and Intestinal immune network for immunoglobulin A production. And four target genes and 87 pathways of the hsa-miR-495 were enriched in PAAD. Interestingly, we found hsa-miR-495 with a low expression having a poor overall survival and significantly different recurrence rate within 5 years.
Hsa-miR-495 and its target genes may serve as a prognostic and predictive marker in PAAD. Further research on the function of the hsa-miR-495 and its target genes in the KEGG pathway may provide references for treatment of PAAD.
胰腺腺癌(PAAD)是世界上最致命的癌症之一,因其早期转移、广泛侵袭且预后较差,5年生存率不到5%。然而,其潜在机制尚不清楚。因此,迫切需要探索用于早期诊断的分子标志物或治疗靶点,以改善PAAD的治疗效果。
我们从癌症基因组图谱(TCGA)数据库中检索了PAAD患者的转录组数据以及临床信息。首先确定与生存时间相关的微小RNA(miRNA)和信使RNA(mRNA),随后进行富集分析(基因本体论[GO]和通路)。还研究了与生存时间相关的miRNA-mRNA之间的关系,以发现PAAD可能的转录调控机制。最后,通过查阅文献和检索数据库,我们发现hsa-miR-495可能在PAAD中发挥了重要作用。
总共发现,在378个miRNA中的146个miRNA以及在17100个mRNA中的580个mRNA与PAAD的生存时间相关,其中包括328个风险mRNA和252个保护性mRNA。888个mRNA-miRNA对与PAAD的生存时间相关,涉及755个mRNA和35个miRNA。我们选择了miRanda数据库中通过靶基因预测的13个miRNA进行进一步研究。在这13个miRNA中,hsa-miR-495被确定为一个良好的生物标志物。通过GO和京都基因与基因组百科全书(KEGG)富集分析,显著富集的通路涉及粘着斑、金黄色葡萄球菌感染以及免疫球蛋白A产生的肠道免疫网络。并且hsa-miR-495的四个靶基因和87条通路在PAAD中富集。有趣的是,我们发现低表达的hsa-miR-495患者总生存期较差,且5年内复发率有显著差异。
hsa-miR-495及其靶基因可能作为PAAD的预后和预测标志物。对hsa-miR-495及其靶基因在KEGG通路中的功能进行进一步研究,可能为PAAD的治疗提供参考。