Disregulation of mir-550 and let-7e in intestinal high-risk localized GIST: A GEIS study.
2014; Lippincott Williams & Wilkins; Volume: 32; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2014.32.15_suppl.10514
ISSN1527-7755
AutoresJosé Antonio López‐Guerrero, Antonio Fernández‐Serra, Sílvia Calabuig-Fariñas, Dolors Sánchez-Izquierdo, A Obrador, José Durán, Luis R. Martinez, Regina Alemany, Javier Martín‐Broto,
Tópico(s)Metastasis and carcinoma case studies
Resumo10514 Background: Risk classification of gastrointestinal stromal tumors (GISTs) is critical owing to adjuvant systemic treatments with tyrosine kinase inhibitors (TKI). Tumor size, mitotic count, location or tumor rupture are used to assess patient prognosis after surgical resection and have been validated for GIST risk stratification. miRNAs have been involved in the pathogenesis and progression of most tumors. The purpose of this study is to characterize and to validate differentially expressed miRNAs from a series of recurrent and non-recurrent intestinal hig-risk GIST patients. Methods: RNA from 14 formalin-fixed and paraffin-embedded (FFPE) intestinal high-risk GIST was extracted and analyzed using the GeneChip miRNA 3.0 Array (Affymetrix). The median of tumor size and mitotic count was 11cm (range: 5-25) and 12.5 (range: 0-113 x50 HPF) respectively. Recurrence [median follow-up: 84 months (1-180)] was reported in 8 patients. Normalization and statistical analysis were performed with Partek Genomic Suite 6.6 software and technical validation was conducted using qRT-PCR. Results: A set of 33 miRNAs was significantly deregulated (p=0.05; FC=2) comparing relapsed and non-relapsed patients. Principal Components Analysis divided the patients into two groups: one that comprised the three largest GIST from relapsed patients, and another group with the other cases. We identified 134 miRNAs as differentially expressed between these two groups (p<0.0001; FC=20). The most significantly downregulated miRNAs were let-7e (FC=-1163,99, p<0.0001), miR-17 (FC= -861,879, p<0.0001), miR-195 (FC= -785,334, p<0.0001), miR-143 (FC= -627,526, p<0.0001) and up regulated miR-550 (FC= 204.173, p<0.0001) and miR-1184 (FC= 184.493, p<0.0001). miR-550 and let-7e were selected for technical validation by qRT-PCR confirming the up- (FC=18.0421) and down-regulation respectively (FC=0.6294). Conclusions: Most of the identified miRNAs are involved in cell cycle control and proliferation. We validated the deregulation of miR-550 and let-7e in large intestinal high-risk GISTs. Further studies in independent series of localized GIST with long follow-up are needed in order to demonstrate the prognostic potential of these miRNAs.
Referência(s)