KRAS mutation status is associated with specific pattern of genes expression in pancreatic adenocarcinoma

Future Oncol. 2015;11(13):1905-17. doi: 10.2217/fon.15.98.

Abstract

Aims: To evaluate potential differences at a molecular level between KRAS mutant tumors (MT) and KRAS wild-type (WT) pancreatic tumors and the biological and prognostic significance of different KRAS mutations.

Materials & methods: Expression of a panel of 29 genes was analyzed in KRAS WT and MT tumors. Effects of KRAS mutation and gene expression levels were assessed on patients' survival.

Results: MUC6 (p = 0.009), HGF (p = 0.011), VEGFR-2 (p = 0.020) and VEGFB (p = 0.026) were significantly more expressed and SMAD4 was less suppressed (p = 0.003) in WT KRAS. Contrariwise, SHH (p = 0.012) and IHH (p = 0.031) were more expressed in MT KRAS patients. No OS difference was found between WT and MT KRAS tumors.

Conclusion: KRAS mutation status seems to identify two different subtypes of pancreatic ductal adenocarcinoma with similar outcome but distinct molecular features and probably different therapeutic targets.

Keywords: KRAS; nucleotide variations; overall survival; pancreatic ductal adenocarcinoma; splicing.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*

Substances

  • KRAS protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins p21(ras)