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Tumor Biology

, Volume 37, Issue 8, pp 10827–10838 | Cite as

Transcriptomic changes associated with DKK4 overexpression in pancreatic cancer cells detected by RNA-Seq

Original Article

Abstract

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.

Keywords

DKK4 Pancreatic cancer RNA sequencing Transcriptome Oncogenes 

Notes

Compliance with ethical standards

Conflict of interest

None

Financial support

This paper is supported by the following grants: National Natural Science Foundation of China (No. 81072439, the National High Technology Research and Development Program of China (863 Program) (No. 2012AA021105), and the Research Special Fund for Public Welfare Industry of Health (No. 201202007). There has been no industrial or pharmaceutical support.

Supplementary material

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Institute of Hepatopancreatobiliary Surgery, Southwest HospitalThird Military Medical UniversityChongqingChina
  2. 2.Organ transplantation centreFirst Affiliated Hospital Sun Yat-sen UniversityGuangzhouChina
  3. 3.Translational Research Laboratory, Department of PathologyStony Brook UniversityStony BrookUSA

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