title: Transcriptomic changes associated with DKK4 overexpression in pancreatic cancer cells detected by RNA-Seq.
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.
authors.affiliation: Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Pan
authors.affiliation: Organ transplantation centre, First Affiliated Hospital Sun Yat-sen University, 58 #, 2nd ZhongShan Road, Guangzhou, GD, 510080, China. tai2004qiang@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tai
authors.affiliation: Translational Research Laboratory, Department of Pathology, Stony Brook University, Stony Brook, NY, 11794, USA. curaman5@hotmail.com.
authors.forename: Jingfang
authors.initials: J
authors.lastname: Ju
authors.affiliation: Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China. whuaizhi@gmail.com.
authors.forename: Huaizhi
authors.initials: H
authors.lastname: Wang
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: C442333:DKK4 protein, human; D036341:Intercellular Signaling Peptides and Proteins
keywords: DKK4; Oncogenes; Pancreatic cancer; RNA sequencing; Transcriptome