Journal of Gastrointestinal & Digestive System
Open Access

Abstract

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, phosphomTOR, 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 TaqManŽ miRNA assays qRT-PCR in these fresh frozen tissues. Results: High protein expression was found for 9 out of 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). 00, 20, 40, 60, 81020406080100120140 Supervivencia (meses) %High Low Conclusions: These data shows that PI3K/AKT/mTOR pathway is activated in tumor tissues of GC and that 4EBP1 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.

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