The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance

Simple item page
dc.contributor.authorTapia, Oscar
dc.contributor.authorRiquelme, Ismael
dc.contributor.authorLeal, Pamela
dc.contributor.authorSandoval, Alejandra
dc.contributor.authorAedo, Susana
dc.contributor.authorWeber, Helga
dc.contributor.authorLetelier, Pablo
dc.contributor.authorBellolio, Enrique
dc.contributor.authorVillaseca, Miguel
dc.contributor.authorGarcia, Patricia
dc.contributor.authorCarlos Roa, Juan
dc.date2014
dc.date.accessioned2021-04-30T16:47:48Z
dc.date.available2021-04-30T16:47:48Z
dc.description.abstractSignaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression of proteins involved in the PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) in tumor and nontumor gastric mucosa from patients with advanced GC. We evaluated 71 tumor and 71 nontumor gastric mucosa samples from advanced GC patients, selected from Hernan Henriquez Aravena Hospital (Temuco, Chile). The targets studied were PI3K, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E, and p-eIF4E. Expression data were correlated with clinicomorphological data. Descriptive and analytical statistics were used (95 % confidence interval, p < 0.05). For survival analyses, the Kaplan-Meier method and the log-rank test were used. PI3K, AKT, p-AKT, p-mTOR, p-4E-BP1, P70S6K1, p-P70S6K1, eIF-4E, and p-eIF-4E proteins were significantly overexpressed in tumor tissue. Conversely, PTEN was underexpressed in tumor tissue, notably in pT3-pT4 tumors (p = 0.02) and tumors with lymph node metastases (p < 0.001). P70S6K1 expression was associated with pT3-pT4 tumors (p = 0.03). Moreover, PI3K (p = 0.004), AKT (p = 0.01), p-AKT (p = 0.01), P70S6K1 (p = 0.04), p-P70S6K1 (p = 0.001), and eIF-4E (p = 0.004) were overexpressed in tumors with lymph node metastases. Low expression of 4E-BP1 was associated with poor overall survival (p = 0.03). Our results suggest that the PI3K/AKT/mTOR pathway is activated in GC, with overexpression in tumor tissue of most of the studied proteins (total and phosphorylated). These might be considered as target for specific targeted therapy in GC.
dc.identifier.citationVIRCHOWS ARCHIV,Vol.465,25-33,2014
dc.identifier.doi10.1007/s00428-014-1588-4
dc.identifier.urihttp://repositoriodigital.uct.cl/handle/10925/3536
dc.language.isoen
dc.publisherSPRINGER
dc.sourceVIRCHOWS ARCHIV
dc.subject.englishAKT
dc.subject.englishmTOR
dc.subject.englishImmunohistochemistry
dc.subject.englishGastric cancer
dc.titleThe PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance
dc.typeArticle
uct.catalogadorWOS
uct.indizacionSCI
Files
Collections
MigraciĆ³n Web of Science