Microarray analysis reveals distinct gene set profiles for gastric and intestinal gastrointestinal stromal tumors

Anticancer Res. 2015 Jun;35(6):3289-98.

Abstract

Aim: We sought to address the mechanisms by which intestinal gastrointestinal stromal tumors (GIST) have a markedly higher risk of recurrence than gastric GISTs.

Materials and methods: Gene expression levels were compared among six primary gastric, three intestinal and six metastatic liver GISTs using cDNA microarray. Protein levels of Slit homolog 2 (SLIT2) were analyzed by immunohistochemistry in 25 primary gastric and 10 intestinal GIST.

Results: Intestinal GIST had gene expression profiles similar to clinically malignant and metastatic GIST. In gene set-enrichment analysis, the gene sets MITOTIC_CELL CYCLE and NEURON_DIFFERENTIATION were up-regulated and down-regulated, respectively, in intestinal GIST compared to gastric GIST. High-risk gastric GISTs and intestinal GIST, expressed similar levels of SLIT2 protein, which were lower than those of low-risk gastric GISTs.

Conclusion: The gene-expression profile of intestinal GISTs was similar to that of metastatic liver GISTs. Besides higher proliferative activity, down-regulation of SLIT2 might be involved in clinically malignant phenotypes of intestinal GIST.

Keywords: Gastrointestinal stromal tumor; SLIT2; intestine; microarray; stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Female
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / pathology
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Nerve Tissue Proteins / biosynthesis
  • Oligonucleotide Array Sequence Analysis / methods*
  • Slit Homolog 2 Protein
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Slit Homolog 2 Protein