Zhang Yu, Dang Yi-Wu, Wang Xiao, Yang Xia, Zhang Rui, Lv Zi-Li, Chen Gang
Department of Pathology, First Affiliated Hospital of Guangxi Medical University6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong UniversityJinan 250012, Shandong Province, China.
Am J Transl Res. 2017 Sep 15;9(9):3904-3917. eCollection 2017.
PVT1 has been reported to be involved in the tumorigenesis and development of different cancers. However, the role of PVT1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we applied gene microarray analysis to detect differentially expressed genes (DEGs) between PVT1 RNAi groups and controls. We initially investigated and confirmed PVT1 expression in HCC using The Cancer Genome Atlas (TCGA). The potential genes and pathways associated with PVT1 were also analyzed. We also performed bioinformatics analyses (Gene Ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) to explore the underlying pathways and networks of these potential genes. We selected DLC1 for further analysis. Based on the TCGA database, PVT1 was markedly up-regulated in HCC, whereas DLC1 was down-regulated. Moreover, PVT1 expression negatively correlated with DLC1 in HCC, an observation that has been further validated in different cohorts with Oncomine. High expression of PVT1 was positively associated with gender, race, vascular invasion and pathological grade in HCC. Additionally, the ROC curve indicated that both PVT1 and DLC1 have high diagnostic value in HCC. We speculated that PVT1 might play a significant role in HCC development and progression via regulation of various pathways and genes, especially DLC1 and the Hippo signaling pathway. However, this mechanism should be confirmed by functional experiments.
据报道,PVT1参与了不同癌症的发生和发展。然而,PVT1在肝细胞癌(HCC)中的作用仍不清楚。在本研究中,我们应用基因芯片分析来检测PVT1 RNA干扰组与对照组之间的差异表达基因(DEG)。我们首先使用癌症基因组图谱(TCGA)研究并确认了PVT1在HCC中的表达。还分析了与PVT1相关的潜在基因和通路。我们还进行了生物信息学分析(基因本体论(GO)、通路、京都基因与基因组百科全书(KEGG)以及网络分析),以探索这些潜在基因的潜在通路和网络。我们选择DLC1进行进一步分析。基于TCGA数据库,PVT1在HCC中显著上调,而DLC1下调。此外,在HCC中PVT1表达与DLC1呈负相关,这一观察结果已在不同队列中通过Oncomine进一步验证。PVT1的高表达与HCC中的性别、种族、血管侵犯和病理分级呈正相关。此外,ROC曲线表明PVT1和DLC1在HCC中均具有较高的诊断价值。我们推测PVT1可能通过调节各种通路和基因,尤其是DLC1和Hippo信号通路,在HCC的发生和发展中发挥重要作用。然而,这一机制应通过功能实验来证实。