Integrative analysis of the inverse expression patterns in pancreas development and cancer progression

Abstract

Background: As the malignant tumor, pancreatic cancer with a meager 5-years survival rate has been widely concerning. However, the molecular mechanisms that result in malignant transformation of pancreatic cells remain elusive.

Aim: To investigate the gene expression profiles in normal or malignant transformed pancreas development.

Methods: MaSigPro and ANOVA were performed on two pancreas development datasets downloaded from the Gene Expression Omnibus database. Six pancreatic cancer datasets collected from TCGA database were used to establish differentially expressed genes related to pancreas development and pancreatic cancer. Moreover, gene clusters with highly similar interpretation patterns between pancreas development and pancreatic cancer progression were established by self-organizing map and singular value decomposition. Additionally, the hypergeometric test was performed to compare the corresponding interpretation patterns. Abnormal regions of metabolic pathway were analyzed using the Sub-pathway-GM method.

Results: This study established the continuously upregulated and downregulated genes at different stages in pancreas development and progression of pancreatic cancer. Through analysis of the differentially expressed genes, we established the inverse and consistent direction development-cancer pattern associations. Based on the application of the Subpathway-GM analysis, we established 17 significant metabolic sub-pathways that were closely associated with pancreatic cancer. Of note, the most significant metabolites sub-pathway was related to glycerophospholipid metabolism.

Conclusion: The inverse and consistent direction development-cancer pattern associations were established. There was a significant correlation in the inverse patterns, but not consistent direction patterns.

Keywords: Inverse pattern; Metabolites subpathway; Pancreas development; Pancreatic cancer.

Figure formula

Figure 1

Continuous differential expression patterns in pancreas development. A: Clustering of human pancreas development genes. In the heat map, green indicates down-regulated, and red indicates up-regulated. In the line graphs, lines represent the tendency of the cluster changes; B: Gene Ontology-Biological Process annotations of the continuously up- and down-regulated genes.

Figure 2

The expression patterns identified from GSE96697. Among these results, up- and downregulated patterns (red, green color labeled) were defined and further analyzed in our study.

Figure 3

The expression patterns identified from six pancreatic cancer datasets. A: Among these results, up- and downregulated patterns (red, blue color labeled) were defined and further analyzed in our study; B: Pie diagram showed the up- and down-regulation genes in each pancreatic cancer dataset.

Figure 4

Integrated analysis of expression patterns in pancreas development and pancreatic cancer progression. A: Comparison of interpretation patterns between pancreas development and cancer progression. Color in each cell indicated the p-value; B: Gene Ontology-Biological Process annotations of the inverse interpretation patterns, including dev-up vs can-dw and dev-dw vs can-up.