Comparative analysis of microRNA expression profiles between human gastrointestinal stromal tumors and extra-gastrointestinal stromal tumors
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Abstract:
Objective:To compare the microRNA expression profiles between gastrointestinal stromal tumors (GISTs) and extra-gastrointestinal stromal tumors (EGISTs), and to evaluate their relationship with primary sites and mutant status of tumors. Methods: Formalin-fixed paraffin-embedded tissues of 5 GISTs and 3 EGISTs were evaluated for differential microRNA (miRNA) expression signatures using Agilent microarrays containing 866 human miRNAs and mutation status of these samples were analyzed by PCR amplification and direct sequencing. Results: Unsupervised hierarchical clustering analysis revealed that 8 samples had been divided into 3 clusters. One gastric GIST and 1 EGIST with the same mutation grouped together and the remaining 2 gastric GISTs also formed a cluster. The other 4 samples including 2 intestinal GISTs and 2 EGISTs could be divided into a third separate cluster. And then we divided 5 GSITs samples into 2 groups according to their anatomical location (stomach and intestine) and assigned 3 EGISTs samples to the group with a similar miRNA expression pattern. Twelve miRNAs, most of which were predicted to participate in the regulation of KIT/PDGFRA signaling, were found to be differentially expressed between the two groups; among them, 5 miRNAs known to be involved in tumor progression were found down-regulated in intestinal group. In addition, only 3 miRNAs were found differentially expressed between GISTs and EGISTs. Conclusion:GISTs and EGISTs have similar miRNA expression patterns related with sites and mutation status; miRNA expression patterns may help to differentiate GISTs at the molecular level.
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Project supported by the National Natural Science Foundation of China (No. 30901735), and the Science and Technology Project of Xi’an \[No. SF1028(4)\]