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Updated: Jun 11, 2025
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
MicroRNA expression signature in gastrointestinal stromal tumour & their molecular & histological features
Abdul Ghani1, Harvinder Singh2,3, Hemanth Kumar4
1Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract:
Background & objectives In gastrointestinal stromal tumour (GIST), not only genetic abnormalities are responsible for adverse clinical events, but epigenetic modifications also play a crucial role. MicroRNA (miRNA) dysregulation plays a significant role in carcinogenesis as miRNAs serve as natural silencer for their targets. Our study aimed to explore the miRNAs expression and its association with molecular and histopathological characteristics of GIST. Methods Fifty GIST samples, including 45 formalin fixed paraffin embedded (FFPE) and fresh tissues were included. Peripheral non-tumour tissues were used as controls. All the cases were confirmed using immunohistochemistry. RNA was extracted using miRNA-specific kit, and the expression was performed using RT-qPCR. The data were evaluated using AriaMx software version 1.5 (Agilent, US). MiRNAs expression was analyzed by using the relative quantification method (ΔΔCT). Results miR-221, miR-222, miR-494 and miR-34a showed significant down-regulation in tumours relative to non-tumour tissues. The expression levels of these miRNAs were significantly down-regulated in c-KIT (proto-oncogene encoding the tyrosine kinase transmembrane receptor)-positive tumours compared to c-KIT-negative. Further analysis revealed that reduced expression was associated with spindle subtypes and gastric localization. However, there was no significant correlation with other histological features. Additionally, miR-221/222, and miR-494 were down-regulated in most of the KIT exon 11 mutant subtypes, while miRNA-34a was associated with platelet derived growth factor receptor alpha (PDGFRA) mutations. Interpretation & conclusions The present study showed that the down-regulation of these miRNAs may help better molecular classification and characterization of GISTs. Our results offer new insight into the association between miRNAs and histological features, enabling a more thorough understanding of GISTs at the molecular level.
Insights
MicroRNA (miRNA) down-regulation is linked to gastrointestinal stromal tumour (GIST) characteristics. Reduced miR-221, miR-222, miR-494, and miR-34a expression correlates with GIST subtypes and mutations, aiding molecular classification.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Gastrointestinal stromal tumour (GIST) development involves genetic and epigenetic factors.
- MicroRNAs (miRNAs) function as tumor suppressors by silencing gene expression.
- Dysregulated miRNA expression is implicated in cancer development, including GIST.
Purpose of the Study:
- To investigate miRNA expression patterns in GIST.
- To correlate miRNA expression with molecular and histopathological features of GIST.
- To explore the role of specific miRNAs in GIST pathogenesis.
Main Methods:
- Analysis of miRNA expression in 50 GIST samples and control tissues using RT-qPCR.
- Confirmation of GIST cases via immunohistochemistry.
- Statistical analysis of miRNA expression relative to c-KIT and PDGFRA mutations, tumor subtype, and localization.
Main Results:
- Significant down-regulation of miR-221, miR-222, miR-494, and miR-34a observed in GIST tissues compared to non-tumour tissues.
- Down-regulated miRNAs showed significant association with c-KIT-positive GISTs.
- Reduced expression of miR-221/222 and miR-494 correlated with KIT exon 11 mutations, while miR-34a was linked to PDGFRA mutations.
- Spindle subtypes and gastric GISTs exhibited reduced miRNA expression.
Conclusions:
- Down-regulation of specific miRNAs (miR-221, miR-222, miR-494, miR-34a) is a key feature in GIST.
- These miRNAs may serve as biomarkers for molecular classification and characterization of GIST.
- Findings provide insights into miRNA involvement in GIST histology and molecular alterations.
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