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Published on: July 3, 2025
Gene expression profiling of human gastrointestinal stromal tumors according to its malignant potential
Keun Hur1, Hyuk-Joon Lee, Jung Hoon Woo
1Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea. dr.keunhur@gmail.com
Purpose:
Surgical removal or treatment with Imatinib mesylate (STI-571/Gleevec) is shown to be highly effective in gastrointestinal stromal tumors (GISTs). However, it is unclear the understanding of the molecular basis in GISTs according to its malignant potential. The aim of this study was therefore to determine the gene expression profiles according to GISTs risk progresses.
Results:
In this study, we performed a cDNA microarray with 30 human GIST tissues using the Mac Array-Express 10K chip (10,800 genes), and compared their gene expression profiles among low (n=10), intermediate (n=8), and high-risk groups (n=12) according to NIH consensus criteria. A total of 181 genes were identified to be expressed differentially according to GISTs risk category. After clustering by self-organizing maps, the expression profiles of 32 genes sequentially increased as the tumor risk increased, and those of 37 genes sequentially decreased as the tumor risk increased. Identified targets have been cross referenced against their involvements in different cellular pathways, according to GenMAPP, KEGG, and BioCarta. In pathway-enrichment analysis, eight up-regulated pathways and ten down-regulated pathways were significantly enriched.
Conclusions:
Our results showed a remarkably distinct and uniform expression pattern in GISTs progression. Moreover, the expression profiling of GISTs may be used as a basic reference to better understand the molecular basis of GISTs tumorigenesis and to identify a novel target molecule for replacing KIT and PDGFRA for a complementary diagnosis and effective curative treatments.
Insights
This study reveals distinct gene expression patterns in gastrointestinal stromal tumors (GISTs) that correlate with risk. These findings offer insights into GISTs tumorigenesis and potential new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Gastrointestinal stromal tumors (GISTs) are effectively treated with surgery or imatinib mesylate.
- The molecular basis of GISTs, particularly concerning malignant potential, requires further elucidation.
- Understanding gene expression profiles linked to GIST risk progression is crucial for improved diagnostics and therapeutics.
Purpose of the Study:
- To determine gene expression profiles in GISTs that correlate with increasing risk categories.
- To identify molecular markers associated with GISTs progression.
- To provide a basis for understanding GISTs tumorigenesis and discovering novel therapeutic targets.
Main Methods:
- cDNA microarray analysis of 30 human GIST tissues (low, intermediate, high-risk groups).
- Utilized Mac Array-Express 10K chip (10,800 genes) and NIH consensus criteria for risk stratification.
- Gene expression data analyzed using self-organizing maps and pathway enrichment analysis (GenMAPP, KEGG, BioCarta).
Main Results:
- Identified 181 differentially expressed genes across GIST risk categories.
- Observed sequential increase in 32 gene expression profiles and decrease in 37 gene expression profiles with increasing tumor risk.
- Pathway enrichment analysis revealed 8 significantly up-regulated and 10 down-regulated pathways.
Conclusions:
- GISTs exhibit distinct and uniform gene expression patterns that change with tumor progression.
- Gene expression profiling of GISTs can serve as a reference for understanding tumorigenesis.
- Identified potential novel target molecules for complementary diagnosis and treatment of GISTs, beyond KIT and PDGFRA.
