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

World J Gastroenterol. 2019 Aug 28;25(32):4727-4738. doi: 10.3748/wjg.v25.i32.4727.

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.

MeSH terms

  • Cell Transformation, Neoplastic / genetics*
  • Datasets as Topic
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / genetics
  • Humans
  • Male
  • Metabolic Networks and Pathways / genetics
  • Oligonucleotide Array Sequence Analysis
  • Pancreas / growth & development*
  • Pancreas / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Trans-Activators / genetics

Substances

  • Homeodomain Proteins
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein