Level of miR-125B and miR-451 and Deregulated Expression of PI3K/AKT/mTOR Pathway in Gastric Cancer
Oscar Tapia, Ismael Riquelme, Alejandra Sandoval, Pablo Letelier, Pamela Leal, Juan Carlos Roa. University of La Frontera, Temuco, Chile
Background: Gastric cancer (GC) is the second most lethal malignancy worldwide and the leading cause of death relating to neoplastic disease in Chile. Authors have reported that PI3K/AKT/mTOR pathway could play an important role in the development of GC, moreover, some microRNAs (miRs) could regulate post-transcriptionally the gene expression of this pathway. The aim of this study was to evaluate both the protein expression of the components of PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) and the expression of miR-125b and miR-451 in a cohort of GC cases.
Design: The protein expression of PI3K/AKT/mTOR was performed by IHC in Tissue microarray of 71 tumors and 71 normal tissues from patients with GC. The proteins were PI3K, PTEN, AKT, phospho-AKT, mTOR, phospho-mTOR, p70S6K, phospho-p70S6K, 4E-BP1, phospho-4E-BP1, eIF4E and phospho-eIF4E. Then the expression of miR-125b and miR-451 was analyzed in 22 hispanic/amerindian GC and 22 control normal using TaqMan® miRNA assays qRT-PCR in these fresh frozen tissues.
Results: High protein expression was found for 9 the 12 proteins in tumor tissue compared with normal tissue (p<0,05).
Conversely, a high expression of PTEN was found in normal tissues (p<0.001). Kaplan-Meier analysis exhibited a poor survival in those patients with low expression of 4E-BP1 (p<0,05).
In miRs analysis, a downregulation of miR-125b and miR-451 was observed in tumor tissues vs paired normal mucosa (p<0.05).
Conclusions: These data show that PI3K/AKT/mTOR pathway is activated in tumor tissues of GC and that 4E-BP1 could be a potential prognosis biomarker in this cancer. Moreover, the downregulation of miR-125b and miR-451 suggests an important role of these miRs in carcinogenesis probably targeting AKT and TSC1 within PI3K/AKT/mTOR pathway. These data could be an initial approach to promote a new therapy strategy on this pathway.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 95, Wednesday Afternoon