Exploration of Exosomal Micro RNA Biomarkers Related to Epithelial-to-Mesenchymal Transition in Pancreatic Cancer

Anticancer Res. 2020 Apr;40(4):1843-1853. doi: 10.21873/anticanres.14138.

Abstract

Background/aim: Epithelial-to-mesenchymal transition (EMT) plays important roles in cancer progression. This study aimed to identify the exosomal miRNA (exo-miRNA) profiles related to the EMT status in pancreatic cancer (PC).

Materials and methods: Comprehensive exo-miRNA-expression profiles in the culture media of PC cell lines were analyzed through microarray technology. The identified miRNAs were analyzed to investigate their clinical implication using The Cancer Genome Atlas (TCGA) dataset and clinical samples.

Results: We prioritized 291 exo-miRNAs differentially expressed between epithelial and mesenchymal cell types. Among them, survival analysis based on the TCGA dataset revealed that mir-196b and mir-204 significantly stratify the prognosis of PC cases. In addition, analysis of cell lines indicated miR-196b-3p as a mesenchymal marker and miR-204-3p as an epithelial marker. Finally, we demonstrated that miR-196b-3p and miR-204-3p in serum exosomes were differentially expressed among intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and PC.

Conclusion: Serum exo-miRNA biomarkers potentially identify the pancreatic tumor status through less-invasive methods.

Keywords: Epithelial-mesenchymal transition; exosomes; micro RNA; pancreatic cancer.

MeSH terms

  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Exosomes / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / blood*
  • Microarray Analysis
  • Neoplasm Staging
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Prognosis

Substances

  • Biomarkers, Tumor
  • MicroRNAs