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. 2019 Aug 13;10(8):612.
doi: 10.3390/genes10080612.

Identification of Key Genes and Pathways in Pancreatic Cancer Gene Expression Profile by Integrative Analysis

Wenzong Lu  1 , Ning Li  2 , Fuyuan Liao  2
Affiliations

Identification of Key Genes and Pathways in Pancreatic Cancer Gene Expression Profile by Integrative Analysis

Wenzong Lu et al. Genes (Basel). .

Abstract

Background: Pancreatic cancer is one of the malignant tumors that threaten human health.

Methods: The gene expression profiles of GSE15471, GSE19650, GSE32676 and GSE71989 were downloaded from the gene expression omnibus database including pancreatic cancer and normal samples. The differentially expressed genes between the two types of samples were identified with the Limma package using R language. The gene ontology functional and pathway enrichment analyses of differentially-expressed genes were performed by the DAVID software followed by the construction of a protein-protein interaction network. Hub gene identification was performed by the plug-in cytoHubba in cytoscape software, and the reliability and survival analysis of hub genes was carried out in The Cancer Genome Atlas gene expression data.

Results: The 138 differentially expressed genes were significantly enriched in biological processes including cell migration, cell adhesion and several pathways, mainly associated with extracellular matrix-receptor interaction and focal adhesion pathway in pancreatic cancer. The top hub genes, namely thrombospondin 1, DNA topoisomerase II alpha, syndecan 1, maternal embryonic leucine zipper kinase and proto-oncogene receptor tyrosine kinase Met were identified from the protein-protein interaction network. The expression levels of hub genes were consistent with data obtained in The Cancer Genome Atlas. DNA topoisomerase II alpha, syndecan 1, maternal embryonic leucine zipper kinase and proto-oncogene receptor tyrosine kinase Met were significantly linked with poor survival in pancreatic adenocarcinoma.

Conclusions: These hub genes may be used as potential targets for pancreatic cancer diagnosis and treatment.

Keywords: bioinformatics; gene expression; hub gene; pancreatic cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Four-set Venn diagram showing the common differentially expressed genes from the four Gene Expression Omnibus series datasets. Differentially expressed genes (DEG) were identified with classical t test, statistically significant DEG were defined with p < 0.01 and log2-fold change (log2FC) >1 or < −1 as the cut-off criterion for every dataset.
Figure 2
Figure 2
Heat map showing up-regulated and down-regulated differentially expressed genes in pancreatic adenocarcinoma compared to the normal samples in the four datasets. The expression values are log2 transformed for absolute value of fold changes (>1 or <−1) between normal tissues and pancreatic adenocarcinoma samples. Green represents down-regulation and red represents up-regulation. (A) GSE15471; (B) GSE19650; (C) GSE32676; (D) GSE71989.
Figure 3
Figure 3
Differentially expressed genes protein–protein interaction (PPI) network was constructed and visualized using Cytoscape software. Red nodes represent up-regulated genes and baby blue nodes represent down-regulated genes in pancreatic adenocarcinoma compared to the normal samples. Only two nodes included one edge and alone node were removed from the network.
Figure 4
Figure 4
Box-whisker plots showing the expression of hub genes in pancreatic adenocarcinoma samples. (A) Proto-oncogene receptor tyrosine kinase Met; (B) Maternal embryonic leucine zipper kinase; (C) syndecan 1; (D) thrombospondin 1; (E) DNA topoisomerase II alpha.
Figure 5
Figure 5
Kaplan–Meier plots showing the association of hub genes expression levels with patient survival. (A) Proto-oncogene receptor tyrosine kinase Met; (B) Maternal embryonic leucine zipper kinase; (C) syndecan 1; (D) thrombospondin 1; (E) DNA topoisomerase II alpha.
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