Ouyang Yongsheng, Pan Juncheng, Tai Qiang, Ju Jingfang, Wang Huaizhi
Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.
Organ transplantation centre, First Affiliated Hospital Sun Yat-sen University, 58 #, 2nd ZhongShan Road, Guangzhou, GD, 510080, China.
Tumour Biol. 2016 Aug;37(8):10827-38. doi: 10.1007/s13277-015-4379-x. Epub 2016 Feb 15.
The promotion of tumor development by Dickkopf 4 (DKK4) is receiving increased attention. However, the association between DKK4 and pancreatic cancer remains unclear. DKK4 expression was measured in pancreatic ductal adenocarcinoma tissues using qRT-PCR and immunohistochemistry. A DKK4-overexpressing pancreatic cancer cell line was established, and the differentially expressed genes (DEGs) that were induced by DKK4 were identified using transcriptome sequencing. The association between the identified DEGs and pancreatic cancer was assessed using gene ontology (GO), pathway analysis, pathway interaction networks, differentially expressed gene interaction network analysis, and co-expression gene networks. Finally, the accuracy of the analyses was validated using serial paraffin and frozen sections of clinical samples. DKK4 is highly expressed in pancreatic cancer tissues. DEGs of overexpression DKK4 of PANC-1 are mostly upregulated. GO and pathway analysis showed that DKK4 are associated with tumor and organ development and immune inflammation. The mitogen-activated protein kinase (MAPK) signaling pathway was the main signal transduction pathway that showed significant enrichment in overexpression DKK4 of PANC-1. The results of GO, pathway analyses, and differentially expressed gene interaction network identified genes that are closely associated with tumor development, including MAPK3, PIK3R3, VAV3, JAG1, and Notch3. The immunohistochemistry and immunofluorescence results suggested that DKK4 is co-expressed with MAPK3 and VAV3 in pancreatic cancer tissues. The results presented here show for the first time that DKK4 is highly expressed in pancreatic cancer tissues. Bioinformatics analysis of a DKK4-overexpressing of PANC-1 identified several oncogenes that are closely associated with tumors, and the MAPK signaling pathway is the core signal transduction pathway. DKK4 can be co-expressed with MAPK3 and VAV3 in pancreatic ductal adenocarcinoma tissues. Thus, DKK4 may have function on the development and progression of pancreatic cancer.
Dickkopf 4（DKK4）对肿瘤发展的促进作用日益受到关注。然而，DKK4与胰腺癌之间的关联仍不清楚。采用qRT-PCR和免疫组织化学方法检测胰腺导管腺癌组织中DKK4的表达。建立了过表达DKK4的胰腺癌细胞系，并通过转录组测序鉴定由DKK4诱导的差异表达基因（DEG）。利用基因本体论（GO）、通路分析、通路相互作用网络、差异表达基因相互作用网络分析和共表达基因网络评估所鉴定的DEG与胰腺癌之间的关联。最后，使用临床样本的连续石蜡切片和冰冻切片验证分析的准确性。DKK4在胰腺癌组织中高表达。PANC-1过表达DKK4的DEG大多上调。GO和通路分析表明，DKK4与肿瘤和器官发育以及免疫炎症相关。丝裂原活化蛋白激酶（MAPK）信号通路是在PANC-1过表达DKK4中显示出显著富集的主要信号转导通路。GO、通路分析和差异表达基因相互作用网络的结果鉴定出与肿瘤发展密切相关的基因，包括MAPK3、PIK3R3、VAV3、JAG1和Notch3。免疫组织化学和免疫荧光结果表明，DKK4在胰腺癌组织中与MAPK3和VAV3共表达。此处呈现的结果首次表明DKK4在胰腺癌组织中高表达。对PANC-1过表达DKK4进行生物信息学分析，鉴定出几个与肿瘤密切相关的癌基因，并且MAPK信号通路是核心信号转导通路。在胰腺导管腺癌组织中，DKK4可与MAPK
